1932
0
  1. Home
  2. A-Z Publications
  3. Annual Review of Immunology
  4. Volume 36, 2018
  5. Article

Annual Review of Immunology

Volume 36, 2018

Complement and the Regulation of T Cell Responses

Abstract

The complement system is an evolutionarily ancient key component of innate immunity required for the detection and removal of invading pathogens. It was discovered more than 100 years ago and was originally defined as a liver-derived, blood-circulating sentinel system that classically mediates the opsonization and lytic killing of dangerous microbes and the initiation of the general inflammatory reaction. More recently, complement has also emerged as a critical player in adaptive immunity via its ability to instruct both B and T cell responses. In particular, work on the impact of complement on T cell responses led to the surprising discoveries that the complement system also functions within cells and is involved in regulating basic cellular processes, predominantly those of metabolic nature. Here, we review current knowledge about complement's role in T cell biology, with a focus on the novel intracellular and noncanonical activities of this ancient system.

Keyword(s): autoimmunity, CD46, complosome, infection, metabolism, Th1 response
Loading

Article metrics loading...

/content/journals/10.1146/annurev-immunol-042617-053245
2018-04-26
2024-04-19
Loading full text...

Full text loading...

/deliver/fulltext/immunol/36/1/annurev-immunol-042617-053245.html?itemId=/content/journals/10.1146/annurev-immunol-042617-053245&mimeType=html&fmt=ahah

Literature Cited

  1. Creagh EM, O'Neill LA. 1.  2006. TLRs, NLRs and RLRs: a trinity of pathogen sensors that co-operate in innate immunity. Trends Immunol 27:352–57 [Google Scholar]
  2. Lavelle EC, Murphy C, O'Neill LA, Creagh EM. 2.  2010. The role of TLRs, NLRs, and RLRs in mucosal innate immunity and homeostasis. Mucosal Immunol 3:17–28 [Google Scholar]
  3. Köhl J. 3.  2006. The role of complement in danger sensing and transmission. Immunol. Res. 34:157–76 [Google Scholar]
  4. Walport M. 4.  2001. Complement. First of two parts. N. Engl. J. Med. 344:1058–66 [Google Scholar]
  5. Walport M. 5.  2001. Complement. Second of two parts. N. Engl. J. Med. 344:1140–44 [Google Scholar]
  6. Latz E, Xiao TS, Stutz A. 6.  2013. Activation and regulation of the inflammasomes. Nat. Rev. Immunol. 13:397–411 [Google Scholar]
  7. Wen H, Miao EA, Ting JP. 7.  2013. Mechanisms of NOD-like receptor–associated inflammasome activation. Immunity 39:432–41 [Google Scholar]
  8. Botto M, Dell'Agnola C, Bygrave AE, Thompson EM, Cook HT. 8.  et al. 1998. Homozygous C1q deficiency causes glomerulonephritis associated with multiple apoptotic bodies. Nat. Genet. 19:56–59 [Google Scholar]
  9. Kohl J. 9.  2006. Self, non-self, and danger: a complementary view. Adv. Exp. Med. Biol. 586:71–94 [Google Scholar]
  10. Flyvbjerg A. 10.  2017. The role of the complement system in diabetic nephropathy. Nat. Rev. Nephrol. 13:311–18 [Google Scholar]
  11. Carroll M. 11.  2004. The complement system in regulation of adaptive immunity. Nat. Immunol. 5:981–86 [Google Scholar]
  12. Kemper C, Atkinson JP. 12.  2007. T-cell regulation: with complements from innate immunity. Nat. Rev. Immunol. 7:9–18 [Google Scholar]
  13. Dunkelberger JR, Song WC. 13.  2010. Complement and its role in innate and adaptive immune responses. Cell Res 20:34–50 [Google Scholar]
  14. Kolev M, Friec GL, Kemper C. 14.  2014. Complement: tapping into new sites and effector systems. Nat. Rev. Immunol. 14:811–20 [Google Scholar]
  15. Kolev M, Kemper C. 15.  2017. Keeping it all going—complement meets metabolism. Front. Immunol. 8:1 [Google Scholar]
  16. Hess C, Kemper C. 16.  2016. Complement-mediated regulation of metabolism and basic cellular processes. Immunity 45:240–54 [Google Scholar]
  17. Arbore G, Kemper C. 17.  2016. A novel “complement-metabolism-inflammasome axis” as a key regulator of immune cell effector function. Eur. J. Immunol. 46:1563–73 [Google Scholar]
  18. Triantafilou M, Hughes TR, Morgan BP, Triantafilou K. 18.  2016. Complementing the inflammasome. Immunology 147:152–64 [Google Scholar]
  19. Kolev M, Dimeloe S, Le Friec G, Navarini A, Arbore G. 19.  et al. 2015. Complement regulates nutrient influx and metabolic reprogramming during Th1 cell responses. Immunity 42:1033–47 [Google Scholar]
  20. Bordet J, Gengou O. 20.  1901. Sur l'existence de substances sensibilisatrices dans la plupart des sérums antimicrobiens Paris: Ann. Inst. Pasteur
  21. Silverstein AM. 21.  1986. Anti-antibodies and anti-idiotype immunoregulation, 1899–1904: the inexorable logic of Paul Ehrlich. Cell. Immunol. 99:507–22 [Google Scholar]
  22. Ricklin D, Hajishengallis G, Yang K, Lambris JD. 22.  2010. Complement: a key system for immune surveillance and homeostasis. Nat. Immunol. 11:785–97 [Google Scholar]
  23. Merle NS, Church SE, Fremeaux-Bacchi V, Roumenina LT. 23.  2015. Complement system part I—molecular mechanisms of activation and regulation. Front. Immunol. 6:262 [Google Scholar]
  24. Merle NS, Noe R, Halbwachs-Mecarelli L, Fremeaux-Bacchi V, Roumenina LT. 24.  2015. Complement system part II: role in immunity. Front. Immunol. 6:257 [Google Scholar]
  25. Liszewski MK, Kolev M, Le Friec G, Leung M, Bertram PG. 25.  et al. 2013. Intracellular complement activation sustains T cell homeostasis and mediates effector differentiation. Immunity 39:1143–57 [Google Scholar]
  26. Kanse SM, Gallenmueller A, Zeerleder S, Stephan F, Rannou O. 26.  et al. 2012. Factor VII–activating protease is activated in multiple trauma patients and generates anaphylatoxin C5a. J. Immunol. 188:2858–65 [Google Scholar]
  27. Huber-Lang M, Denk S, Fulda S, Erler E, Kalbitz M. 27.  et al. 2012. Cathepsin D is released after severe tissue trauma in vivo and is capable of generating C5a in vitro. Mol. Immunol. 50:60–65 [Google Scholar]
  28. Newman SL, Becker S, Halme J. 28.  1985. Phagocytosis by receptors for C3b (CR1), iC3b (CR3), and IgG (Fc) on human peritoneal macrophages. J. Leukoc. Biol. 38:267–78 [Google Scholar]
  29. Le Friec G, Friec G, Kemper C. 29.  2009. Complement: coming full circle. Arch. Immunol. Ther. Exp. 57:393–407 [Google Scholar]
  30. Monk PN, Scola AM, Madala P, Fairlie DP. 30.  2007. Function, structure and therapeutic potential of complement C5a receptors. Br. J. Pharmacol. 152:429–48 [Google Scholar]
  31. Klos A, Tenner A, Johswich K, Ager R, Reis E, Köhl J. 31.  2009. The role of the anaphylatoxins in health and disease. Mol. Immunol. 46:2753–66 [Google Scholar]
  32. Manthey HD, Woodruff TM, Taylor SM, Monk PN. 32.  2009. Complement component 5a (C5a). Int. J. Biochem. Cell Biol. 41:2114–17 [Google Scholar]
  33. Sarma JV, Ward PA. 33.  2012. New developments in C5a receptor signaling. Cell Health Cytoskelet 4:73–82 [Google Scholar]
  34. Mayilyan KR. 34.  2012. Complement genetics, deficiencies, and disease associations. Protein Cell 3:487–96 [Google Scholar]
  35. Webb J, Whaley K. 35.  1986. Complement and immune complex diseases. Aust. N. Z. J. Med. 16:268–78 [Google Scholar]
  36. Boackle SA, Holers VM. 36.  2003. Role of complement in the development of autoimmunity. Curr. Dir. Autoimmun. 6:154–68 [Google Scholar]
  37. Martínez-Barricarte R, Heurich M, Valdes-Cañedo F, Vazquez-Martul E, Torreira E. 37.  et al. 2010. Human C3 mutation reveals a mechanism of dense deposit disease pathogenesis and provides insights into complement activation and regulation. J. Clin. Investig. 120:3702–12 [Google Scholar]
  38. Korb LC, Ahearn JM. 38.  1997. C1q binds directly and specifically to surface blebs of apoptotic human keratinocytes: complement deficiency and systemic lupus erythematosus revisited. J. Immunol. 158:4525–28 [Google Scholar]
  39. Ghebrehiwet B, Peerschke EI. 39.  2004. Role of C1q and C1q receptors in the pathogenesis of systemic lupus erythematosus. Curr. Dir. Autoimmun. 7:87–97 [Google Scholar]
  40. Zipfel PF, Skerka C. 40.  2009. Complement regulators and inhibitory proteins. Nat. Rev. Immunol. 9:729–40 [Google Scholar]
  41. Meri S, Jarva H. 41.  1998. Complement regulation. Vox Sang 74:Suppl. 2291–302 [Google Scholar]
  42. Schmidt CQ, Lambris JD, Ricklin D. 42.  2016. Protection of host cells by complement regulators. Immunol. Rev. 274:152–71 [Google Scholar]
  43. Naughton MA, Botto M, Carter MJ, Alexander GJ, Goldman JM, Walport MJ. 43.  1996. Extrahepatic secreted complement C3 contributes to circulating C3 levels in humans. J. Immunol. 156:3051–56 [Google Scholar]
  44. Naughton MA, Walport MJ, Würzner R, Carter MJ, Alexander GJ. 44.  et al. 1996. Organ-specific contribution to circulating C7 levels by the bone marrow and liver in humans. Eur. J. Immunol. 26:2108–12 [Google Scholar]
  45. Passwell J, Schreiner GF, Nonaka M, Beuscher HU, Colten HR. 45.  1988. Local extrahepatic expression of complement genes C3, factor B, C2, and C4 is increased in murine lupus nephritis. J. Clin. Investig. 82:1676–84 [Google Scholar]
  46. Morgan B, Gasque P. 46.  1997. Extrahepatic complement biosynthesis: where, when and why?. Clin. Exp. Immunol. 107:1–7 [Google Scholar]
  47. Barnum S. 47.  1995. Complement biosynthesis in the central nervous system. Crit. Rev. Oral Biol. Med. 6:132–46 [Google Scholar]
  48. Circolo A, Pierce GF, Katz Y, Strunk RC. 48.  1990. Antiinflammatory effects of polypeptide growth factors: platelet-derived growth factor, epidermal growth factor, and fibroblast growth factor inhibit the cytokine-induced expression of the alternative complement pathway activator factor B in human fibroblasts. J. Biol. Chem. 265:5066–71 [Google Scholar]
  49. Gerritsma JS, van Kooten C, Gerritsen AF, van Es LA, Daha MR. 49.  1998. Transforming growth factor-beta 1 regulates chemokine and complement production by human proximal tubular epithelial cells. Kidney Int 53:609–16 [Google Scholar]
  50. Gadjeva M, Verschoor A, Brockman MA, Jezak H, Shen LM. 50.  et al. 2002. Macrophage-derived complement component C4 can restore humoral immunity in C4-deficient mice. J. Immunol. 169:5489–95 [Google Scholar]
  51. Pratt JR, Basheer SA, Sacks SH. 51.  2002. Local synthesis of complement component C3 regulates acute renal transplant rejection. Nat. Med. 8:582–87 [Google Scholar]
  52. Liu J, Miwa T, Hilliard B, Chen Y, Lambris J. 52.  et al. 2005. The complement inhibitory protein DAF (CD55) suppresses T cell immunity in vivo. J. Exp. Med. 201:567–77 [Google Scholar]
  53. Song WC. 53.  2012. Crosstalk between complement and Toll-like receptors. Toxicol. Pathol. 40:174–82 [Google Scholar]
  54. Heeger P, Lalli P, Lin F, Valujskikh A, Liu J. 54.  et al. 2005. Decay-accelerating factor modulates induction of T cell immunity. J. Exp. Med. 201:1523–30 [Google Scholar]
  55. Lalli PN, Strainic MG, Yang M, Lin F, Medof ME, Heeger PS. 55.  2008. Locally produced C5a binds to T cell–expressed C5aR to enhance effector T-cell expansion by limiting antigen-induced apoptosis. Blood 112:1759–66 [Google Scholar]
  56. Strainic MG, Liu J, Huang D, An F, Lalli PN. 56.  et al. 2008. Locally produced complement fragments C5a and C3a provide both costimulatory and survival signals to naive CD4+ T cells. Immunity 28:425–35 [Google Scholar]
  57. Pavlov V, Raedler H, Yuan S, Leisman S, Kwan WH. 57.  et al. 2008. Donor deficiency of decay-accelerating factor accelerates murine T cell–mediated cardiac allograft rejection. J. Immunol. 181:4580–89 [Google Scholar]
  58. Le Friec G, Sheppard D, Whiteman P, Karsten CM, Shamoun SA. 58.  et al. 2012. The CD46-Jagged1 interaction is critical for human TH1 immunity. Nat. Immunol. 13:1213–21 [Google Scholar]
  59. Ghannam A, Fauquert JL, Thomas C, Kemper C, Drouet C. 59.  2014. Human complement C3 deficiency: Th1 induction requires T cell–derived complement C3a and CD46 activation. Mol. Immunol. 58:98–107 [Google Scholar]
  60. Liszewski MK, Kolev M, Le Friec G Leung M, Bertram PG. 60.  et al. 2013. Intracellular complement activation sustains T cell homeostasis and mediates effector differentiation. Immunity 39:1143–57 [Google Scholar]
  61. Arbore G, West EE, Spolski R, Robertson AA, Klos A. 61.  et al. 2016. T helper 1 immunity requires complement-driven NLRP3 inflammasome activity in CD4+ T cells. Science 352:aad1210 [Google Scholar]
  62. Elvington M, Liszewski MK, Bertram P, Kulkarni HS, Atkinson JP. 62.  2017. A C3(H2O) recycling pathway is a component of the intracellular complement system. J. Clin. Investig. 127:970–81 [Google Scholar]
  63. Arbore G, Kemper C, Kolev M. 63.  2017. Intracellular complement—the complosome—in immune cell regulation. Mol. Immunol. 89:2–9 [Google Scholar]
  64. Satyam A, Kannan L, Matsumoto N, Geha M, Lapchak PH. 64.  et al. 2017. Intracellular activation of complement 3 is responsible for intestinal tissue damage during mesenteric ischemia. J. Immunol. 198:788–97 [Google Scholar]
  65. Carroll MC, Isenman DE. 65.  2012. Regulation of humoral immunity by complement. Immunity 37:199–207 [Google Scholar]
  66. Carter RH, Fearon DT. 66.  1992. CD19: lowering the threshold for antigen receptor stimulation of B lymphocytes. Science 256:105–7 [Google Scholar]
  67. Dempsey PW, Allison ME, Akkaraju S, Goodnow CC, Fearon DT. 67.  1996. C3d of complement as a molecular adjuvant: bridging innate and acquired immunity. Science 271:348–50 [Google Scholar]
  68. Dempsey PW, Fearon DT. 68.  1996. Complement: instructing the acquired immune system through the CD21/CD19 complex. Res. Immunol. 147:71–75 [Google Scholar]
  69. Pepys MB. 69.  1974. Role of complement in induction of antibody production in vivo: effect of cobra factor and other C3-reactive agents on thymus-dependent and thymus-independent antibody responses. J. Exp. Med. 140:126–45 [Google Scholar]
  70. Pepys MB, Butterworth AE. 70.  1974. Inhibition by C3 fragments of C3-dependent rosette formation and antigen-induced lymphocyte transformation. Clin. Exp. Immunol. 18:273–82 [Google Scholar]
  71. Hebell T, Ahearn JM, Fearon DT. 71.  1991. Suppression of the immune response by a soluble complement receptor of B lymphocytes. Science 254:102–5 [Google Scholar]
  72. Molina H, Holers VM, Li B, Fung Y, Mariathasan S. 72.  et al. 1996. Markedly impaired humoral immune response in mice deficient in complement receptors 1 and 2. PNAS 93:3357–61 [Google Scholar]
  73. Okura Y, Kobayashi I, Yamada M, Sasaki S, Yamada Y. 73.  et al. 2016. Clinical characteristics and genotype-phenotype correlations in C3 deficiency. J. Allergy Clin. Immunol. 137:640–44.e1 [Google Scholar]
  74. Fleming SD, Shea-Donohue T, Guthridge JM, Kulik L, Waldschmidt TJ. 74.  et al. 2002. Mice deficient in complement receptors 1 and 2 lack a tissue injury–inducing subset of the natural antibody repertoire. J. Immunol. 169:2126–33 [Google Scholar]
  75. Heesters BA, Chatterjee P, Kim YA, Gonzalez SF, Kuligowski MP. 75.  et al. 2013. Endocytosis and recycling of immune complexes by follicular dendritic cells enhances B cell antigen binding and activation. Immunity 38:1164–75 [Google Scholar]
  76. Fischer MB, Goerg S, Shen L, Prodeus AP, Goodnow CC. 76.  et al. 1998. Dependence of germinal center B cells on expression of CD21/CD35 for survival. Science 280:582–85 [Google Scholar]
  77. Pappworth IY, Hayes C, Dimmick J, Morgan BP, Holers VM, Marchbank KJ. 77.  2012. Mice expressing human CR1/CD35 have an enhanced humoral immune response to T-dependent antigens but fail to correct the effect of premature human CR2 expression. Immunobiology 217:147–57 [Google Scholar]
  78. Dunkelberger JR, Song WC. 78.  2010. Role and mechanism of action of complement in regulating T cell immunity. Mol. Immunol. 47:2176–86 [Google Scholar]
  79. Clarke EV, Tenner AJ. 79.  2014. Complement modulation of T cell immune responses during homeostasis and disease. J. Leukoc. Biol. 96:745–56 [Google Scholar]
  80. Kolev M, Le Friec G, Kemper C. 80.  2013. The role of complement in CD4+ T cell homeostasis and effector functions. Semin. Immunol. 25:12–19 [Google Scholar]
  81. Kopf M, Abel B, Gallimore A, Carroll M, Bachmann MF. 81.  2002. Complement component C3 promotes T-cell priming and lung migration to control acute influenza virus infection. Nat. Med. 8:373–78 [Google Scholar]
  82. Suresh M, Molina H, Salvato MS, Mastellos D, Lambris JD, Sandor M. 82.  2003. Complement component 3 is required for optimal expansion of CD8 T cells during a systemic viral infection. J. Immunol. 170:788–94 [Google Scholar]
  83. Kim AH, Dimitriou ID, Holland MC, Mastellos D, Mueller YM. 83.  et al. 2004. Complement C5a receptor is essential for the optimal generation of antiviral CD8+ T cell responses. J. Immunol. 173:2524–29 [Google Scholar]
  84. Gancevici GG. 84.  1993. Role of complement inhibition in topical therapy of muco-cutaneous herpes simplex virus infections. Roum. Arch. Microbiol. Immunol. 52:293–303 [Google Scholar]
  85. Zhou W, Peng Q, Li K, Sacks SH. 85.  2007. Role of dendritic cell synthesis of complement in the allospecific T cell response. Mol. Immunol. 44:57–63 [Google Scholar]
  86. Baudino L, Sardini A, Ruseva MM, Fossati-Jimack L, Cook HT. 86.  et al. 2014. C3 opsonization regulates endocytic handling of apoptotic cells resulting in enhanced T-cell responses to cargo-derived antigens. PNAS 111:1503–8 [Google Scholar]
  87. Tam JC, Bidgood SR, McEwan WA, James LC. 87.  2014. Intracellular sensing of complement C3 activates cell autonomous immunity. Science 345:1256070 [Google Scholar]
  88. Li K, Anderson KJ, Peng Q, Noble A, Lu B. 88.  et al. 2008. Cyclic AMP plays a critical role in C3a-receptor-mediated regulation of dendritic cells in antigen uptake and T-cell stimulation. Blood 112:5084–94 [Google Scholar]
  89. Croker DE, Halai R, Kaeslin G, Wende E, Fehlhaber B. 89.  et al. 2014. C5a2 can modulate ERK1/2 signaling in macrophages via heteromer formation with C5a1 and β-arrestin recruitment. Immunol. Cell Biol. 92:631–39 [Google Scholar]
  90. Kastl SP, Speidl WS, Kaun C, Rega G, Assadian A. 90.  et al. 2006. The complement component C5a induces the expression of plasminogen activator inhibitor-1 in human macrophages via NF-κB activation. J. Thromb. Haemost. 4:1790–97 [Google Scholar]
  91. Hashimoto M, Hirota K, Yoshitomi H, Maeda S, Teradaira S. 91.  et al. 2010. Complement drives Th17 cell differentiation and triggers autoimmune arthritis. J. Exp. Med. 207:1135–43 [Google Scholar]
  92. Grailer JJ, Bosmann M, Ward PA. 92.  2012. Regulatory effects of C5a on IL-17A, IL-17F, and IL-23. Front. Immunol. 3:387 [Google Scholar]
  93. Li K, Fazekasova H, Wang N, Peng Q, Sacks SH. 93.  et al. 2012. Functional modulation of human monocytes derived DCs by anaphylatoxins C3a and C5a. Immunobiology 217:65–73 [Google Scholar]
  94. Karp CL, Grupe A, Schadt E, Ewart SL, Keane-Moore M. 94.  et al. 2000. Identification of complement factor 5 as a susceptibility locus for experimental allergic asthma. Nat. Immunol. 1:221–26 [Google Scholar]
  95. Drouin SM, Sinha M, Sfyroera G, Lambris JD, Wetsel RA. 95.  2006. A protective role for the fifth complement component (C5) in allergic airway disease. Am. J. Respir. Crit. Care Med. 173:852–57 [Google Scholar]
  96. Ghannam A, Pernollet M, Fauquert JL, Monnier N, Ponard D. 96.  et al. 2008. Human C3 deficiency associated with impairments in dendritic cell differentiation, memory B cells, and regulatory T cells. J. Immunol. 181:5158–66 [Google Scholar]
  97. Weaver DJ, Reis ES, Pandey MK, Köhl G, Harris N. 97.  et al. 2010. C5a receptor–deficient dendritic cells promote induction of Treg and Th17 cells. Eur. J. Immunol. 40:710–21 [Google Scholar]
  98. Lajoie S, Lewkowich IP, Suzuki Y, Clark JR, Sproles AA. 98.  et al. 2010. Complement-mediated regulation of the IL-17A axis is a central genetic determinant of the severity of experimental allergic asthma. Nat. Immunol. 11:928–35 [Google Scholar]
  99. Cheng SC, Sprong T, Joosten LA, van der Meer JW, Kullberg BJ. 99.  et al. 2012. Complement plays a central role in Candida albicans–induced cytokine production by human PBMCs. Eur. J. Immunol. 42:993–1004 [Google Scholar]
  100. Asgari E, Le Friec G, Yamamoto H, Perucha E, Sacks SS. 100.  et al. 2013. C3a modulates IL-1β secretion in human monocytes by regulating ATP efflux and subsequent NLRP3 inflammasome activation. Blood 122:3473–81 [Google Scholar]
  101. Vaknin-Dembinsky A, Murugaiyan G, Hafler DA, Astier AL, Weiner HL. 101.  2008. Increased IL-23 secretion and altered chemokine production by dendritic cells upon CD46 activation in patients with multiple sclerosis. J. Neuroimmunol. 195:140–45 [Google Scholar]
  102. Kurita-Taniguchi M, Fukui A, Hazeki K, Hirano A, Tsuji S. 102.  et al. 2000. Functional modulation of human macrophages through CD46 (measles virus receptor): production of IL-12 p40 and nitric oxide in association with recruitment of protein-tyrosine phosphatase SHP-1 to CD46. J. Immunol. 165:5143–52 [Google Scholar]
  103. Wang X, Zhang D, Sjolinder M, Wan Y, Sjolinder H. 103.  2017. CD46 accelerates macrophage-mediated host susceptibility to meningococcal sepsis in a murine model. Eur. J. Immunol. 47:119–30 [Google Scholar]
  104. Foley JH, Peterson EA, Lei V, Wan LW, Krisinger MJ, Conway EM. 104.  2015. Interplay between fibrinolysis and complement: Plasmin cleavage of iC3b modulates immune responses. J. Thromb. Haemost. 13:610–18 [Google Scholar]
  105. Csomor E, Bajtay Z, Sandor N, Kristof K, Arlaud GJ. 105.  et al. 2007. Complement protein C1q induces maturation of human dendritic cells. Mol. Immunol. 44:3389–97 [Google Scholar]
  106. Benoit ME, Clarke EV, Morgado P, Fraser DA, Tenner AJ. 106.  2012. Complement protein C1q directs macrophage polarization and limits inflammasome activity during the uptake of apoptotic cells. J. Immunol. 188:5682–93 [Google Scholar]
  107. Clarke EV, Weist BM, Walsh CM, Tenner AJ. 107.  2015. Complement protein C1q bound to apoptotic cells suppresses human macrophage and dendritic cell–mediated Th17 and Th1 T cell subset proliferation. J. Leukoc. Biol. 97:147–60 [Google Scholar]
  108. Strainic MG, Shevach EM, An F, Lin F, Medof ME. 108.  2013. Absence of signaling into CD4+ cells via C3aR and C5aR enables autoinductive TGF-β1 signaling and induction of Foxp3+ regulatory T cells. Nat. Immunol. 14:162–71 [Google Scholar]
  109. Le Friec G, Köhl J, Kemper C. 109.  2013. A complement a day keeps the Fox(p3) away. Nat. Immunol. 14:110–12 [Google Scholar]
  110. Kwan WH, van der Touw W, Paz-Artal E, Li MO, Heeger PS. 110.  2013. Signaling through C5a receptor and C3a receptor diminishes function of murine natural regulatory T cells. J. Exp. Med. 210:257–68 [Google Scholar]
  111. Sohn JH, Bora PS, Suk HJ, Molina H, Kaplan HJ, Bora NS. 111.  2003. Tolerance is dependent on complement C3 fragment iC3b binding to antigen-presenting cells. Nat. Med. 9:206–12 [Google Scholar]
  112. Olivar R, Luque A, Cardenas-Brito S, Naranjo-Gomez M, Blom AM. 112.  et al. 2016. The complement inhibitor factor H generates an anti-inflammatory and tolerogenic state in monocyte-derived dendritic cells. J. Immunol. 196:4274–90 [Google Scholar]
  113. Martin M, Leffler J, Smolag KI, Mytych J, Bjork A. 113.  et al. 2016. Factor H uptake regulates intracellular C3 activation during apoptosis and decreases the inflammatory potential of nucleosomes. Cell Death Differ 23:903–11 [Google Scholar]
  114. Sacks SH. 114.  2010. Complement fragments C3a and C5a: the salt and pepper of the immune response. Eur. J. Immunol. 40:668–70 [Google Scholar]
  115. Wilson JG, Tedder TF, Fearon DT. 115.  1983. Characterization of human T lymphocytes that express the C3b receptor. J. Immunol. 131:684–89 [Google Scholar]
  116. Yaskanin DD, Thompson LF, Waxman FJ. 116.  1992. Distribution and quantitative expression of the complement receptor type 1 (CR1) on human peripheral blood T lymphocytes. Cell Immunol 142:159–76 [Google Scholar]
  117. Torok K, Dezso B, Bencsik A, Uzonyi B, Erdei A. 117.  2015. Complement receptor type 1 (CR1/CD35) expressed on activated human CD4+ T cells contributes to generation of regulatory T cells. Immunol. Lett. 164:117–24 [Google Scholar]
  118. Mouhoub A, Delibrias CC, Fischer E, Boyer V, Kazatchkine MD. 118.  1996. Ligation of CR1 (C3b receptor, CD35) on CD4+ T lymphocytes enhances viral replication in HIV-infected cells. Clin. Exp. Immunol. 106:297–303 [Google Scholar]
  119. Pekalski ML, Garcia AR, Ferreira RC, Rainbow DB, Smyth DJ. 119.  et al. 2016. Recent thymic emigrants produce antimicrobial IL-8, express complement receptors and are precursors of a tissue-homing Th8 lineage of memory cells. bioRxiv 059535. https://doi.org/10.1101/059535 [Crossref]
  120. Kerekes K, Prechl J, Bajtay Z, Jozsi M, Erdei A. 120.  1998. A further link between innate and adaptive immunity: C3 deposition on antigen-presenting cells enhances the proliferation of antigen-specific T cells. Int. Immunol. 10:1923–30 [Google Scholar]
  121. Chen A, Gaddipati S, Hong Y, Volkman DJ, Peerschke EI, Ghebrehiwet B. 121.  1994. Human T cells express specific binding sites for C1q: role in T cell activation and proliferation. J. Immunol. 153:1430–40 [Google Scholar]
  122. Jiang K, Chen Y, Jarvis JN. 122.  2004. Cord blood and adult T cells show different responses to C1q-bearing immune complexes. Cell. Immunol. 229:62–67 [Google Scholar]
  123. Clarke EV, Tenner AJ. 123.  2014. Complement modulation of T cell immune responses during homeostasis and disease. J. Leukoc. Biol. 96:745–56 [Google Scholar]
  124. Raedler H, Vieyra MB, Leisman S, Lakhani P, Kwan W. 124.  et al. 2011. Anti-complement component C5 mAb synergizes with CTLA4Ig to inhibit alloreactive T cells and prolong cardiac allograft survival in mice. Am. J. Transplant. 11:1397–406 [Google Scholar]
  125. van der Touw W, Cravedi P, Kwan WH, Paz-Artal E, Merad M, Heeger PS. 125.  2013. Cutting edge: Receptors for C3a and C5a modulate stability of alloantigen-reactive induced regulatory T cells. J. Immunol. 190:5921–25 [Google Scholar]
  126. Heeger PS, Kemper C. 126.  2012. Novel roles of complement in T effector cell regulation. Immunobiology 217:216–24 [Google Scholar]
  127. Hawksworth OA, Coulthard LG, Woodruff TM. 127.  2017. Complement in the fundamental processes of the cell. Mol. Immunol. 84:17–25 [Google Scholar]
  128. Korty PE, Brando C, Shevach EM. 128.  1991. CD59 functions as a signal-transducing molecule for human T cell activation. J. Immunol. 146:4092–98 [Google Scholar]
  129. Laudisi F, Spreafico R, Evrard M, Hughes TR, Mandriani B. 129.  et al. 2013. Cutting edge: the NLRP3 inflammasome links complement-mediated inflammation and IL-1β release. J. Immunol. 191:1006–10 [Google Scholar]
  130. Liszewski M, Post T, Atkinson J. 130.  1991. Membrane cofactor protein (MCP or CD46): newest member of the regulators of complement activation gene cluster. Annu. Rev. Immunol. 9:431–55 [Google Scholar]
  131. Riley RC, Kemper C, Leung M, Atkinson JP. 131.  2002. Characterization of human membrane cofactor protein (MCP; CD46) on spermatozoa. Mol. Reprod. Dev. 62:534–46 [Google Scholar]
  132. Liszewski MK, Kemper C, Price JD, Atkinson JP. 132.  2005. Emerging roles and new functions of CD46. Springer Semin. Immunopathol. 27:345–58 [Google Scholar]
  133. Cattaneo R. 133.  2004. Four viruses, two bacteria, and one receptor: membrane cofactor protein (CD46) as pathogens' magnet. J. Virol. 78:4385–88 [Google Scholar]
  134. Astier A, Trescol-Biémont MC, Azocar O, Lamouille B, Rabourdin-Combe C. 134.  2000. Cutting edge: CD46, a new costimulatory molecule for T cells, that induces p120CBL and LAT phosphorylation. J. Immunol. 164:6091–95 [Google Scholar]
  135. Kemper C, Chan A, Green J, Brett K, Murphy K, Atkinson J. 135.  2003. Activation of human CD4+ cells with CD3 and CD46 induces a T-regulatory cell 1 phenotype. Nature 421:388–92 [Google Scholar]
  136. Cardone J, Le Friec G, Vantourout P, Roberts A, Fuchs A. 136.  et al. 2010. Complement regulator CD46 temporally regulates cytokine production by conventional and unconventional T cells. Nat. Immunol. 11:862–71 [Google Scholar]
  137. Tsujimura A, Shida K, Kitamura M, Nomura M, Takeda J. 137.  et al. 1998. Molecular cloning of a murine homologue of membrane cofactor protein (CD46): preferential expression in testicular germ cells. Biochem. J. 330:Pt. 1163–68 [Google Scholar]
  138. Yamamoto H, Fara AF, Dasgupta P, Kemper C. 138.  2013. CD46: the ‘multitasker’ of complement proteins. Int. J. Biochem. Cell Biol. 45:2808–20 [Google Scholar]
  139. Liszewski MK, Atkinson JP. 139.  1996. Membrane cofactor protein (MCP; CD46). Isoforms differ in protection against the classical pathway of complement. J. Immunol. 156:4415–21 [Google Scholar]
  140. Ni Choileain S, Weyand NJ, Neumann C, Thomas J, So M, Astier AL. 140.  2011. The dynamic processing of CD46 intracellular domains provides a molecular rheostat for T cell activation. PLOS ONE 6:e16287 [Google Scholar]
  141. Zaffran Y, Destaing O, Roux A, Ory S, Nheu T. 141.  et al. 2001. CD46/CD3 costimulation induces morphological changes of human T cells and activation of Vav, Rac, and extracellular signal–regulated kinase mitogen-activated protein kinase. J. Immunol. 167:6780–85 [Google Scholar]
  142. Liao W, Lin JX, Leonard WJ. 142.  2011. IL-2 family cytokines: new insights into the complex roles of IL-2 as a broad regulator of T helper cell differentiation. Curr. Opin. Immunol. 23:598–604 [Google Scholar]
  143. Liao W, Lin JX, Leonard WJ. 143.  2013. Interleukin-2 at the crossroads of effector responses, tolerance, and immunotherapy. Immunity 38:13–25 [Google Scholar]
  144. Zheng R, Wang L, Fan J, Zhou Q. 144.  2009. Inhibition of PKHD1 may cause S-phase entry via mTOR signaling pathway. Cell Biol. Int. 33:926–33 [Google Scholar]
  145. MacIver NJ, Michalek RD, Rathmell JC. 145.  2013. Metabolic regulation of T lymphocytes. Annu. Rev. Immunol. 31:259–83 [Google Scholar]
  146. Gubser PM, Bantug GR, Razik L, Fischer M, Dimeloe S. 146.  et al. 2013. Rapid effector function of memory CD8+ T cells requires an immediate-early glycolytic switch. Nat. Immunol. 14:1064–72 [Google Scholar]
  147. Pearce EL, Poffenberger MC, Chang CH, Jones RG. 147.  2013. Fueling immunity: insights into metabolism and lymphocyte function. Science 342:1242454 [Google Scholar]
  148. van der Windt GJ, Pearce EL. 148.  2012. Metabolic switching and fuel choice during T-cell differentiation and memory development. Immunol. Rev. 249:27–42 [Google Scholar]
  149. van der Windt GJ, Everts B, Chang CH, Curtis JD, Freitas TC. 149.  et al. 2012. Mitochondrial respiratory capacity is a critical regulator of CD8+ T cell memory development. Immunity 36:68–78 [Google Scholar]
  150. Powell JD, Delgoffe GM. 150.  2010. The mammalian target of rapamycin: linking T cell differentiation, function, and metabolism. Immunity 33:301–11 [Google Scholar]
  151. Cunningham JT, Rodgers JT, Arlow DH, Vazquez F, Mootha VK, Puigserver P. 151.  2007. mTOR controls mitochondrial oxidative function through a YY1-PGC-1α transcriptional complex. Nature 450:736–40 [Google Scholar]
  152. Delgoffe GM, Pollizzi KN, Waickman AT, Heikamp E, Meyers DJ. 152.  et al. 2011. The kinase mTOR regulates the differentiation of helper T cells through the selective activation of signaling by mTORC1 and mTORC2. Nat. Immunol. 12:295–303 [Google Scholar]
  153. Zheng Y, Collins SL, Lutz MA, Allen AN, Kole TP. 153.  et al. 2007. A role for mammalian target of rapamycin in regulating T cell activation versus anergy. J. Immunol. 178:2163–70 [Google Scholar]
  154. Chang CH, Curtis JD, Maggi LB, Faubert B, Villarino AV. 154.  et al. 2013. Posttranscriptional control of T cell effector function by aerobic glycolysis. Cell 153:1239–51 [Google Scholar]
  155. Frauwirth KA, Riley JL, Harris MH, Parry RV, Rathmell JC. 155.  et al. 2002. The CD28 signaling pathway regulates glucose metabolism. Immunity 16:769–77 [Google Scholar]
  156. Powell JD, Pollizzi KN, Heikamp EB, Horton MR. 156.  2012. Regulation of immune responses by mTOR. Annu. Rev. Immunol. 30:39–68 [Google Scholar]
  157. Sena LA, Li S, Jairaman A, Prakriya M, Ezponda T. 157.  et al. 2013. Mitochondria are required for antigen-specific T cell activation through reactive oxygen species signaling. Immunity 38:225–36 [Google Scholar]
  158. Stummvoll GH, DiPaolo RJ, Huter EN, Davidson TS, Glass D. 158.  et al. 2008. Th1, Th2, and Th17 effector T cell–induced autoimmune gastritis differs in pathological pattern and in susceptibility to suppression by regulatory T cells. J. Immunol. 181:1908–16 [Google Scholar]
  159. Astier AL, Meiffren G, Freeman S, Hafler DA. 159.  2006. Alterations in CD46-mediated Tr1 regulatory T cells in patients with multiple sclerosis. J. Clin. Investig. 116:3252–57 [Google Scholar]
  160. Tang SJ, Luo S, Ho JX, Ly PT, Goh E, Roca X. 160.  2016. Characterization of the regulation of CD46 RNA alternative splicing. J. Biol. Chem. 291:14311–23 [Google Scholar]
  161. Karosi T, Szalmas A, Csomor P, Konya J, Petko M, Sziklai I. 161.  2008. Disease-associated novel CD46 splicing variants and pathologic bone remodeling in otosclerosis. Laryngoscope 118:1669–76 [Google Scholar]
  162. Zielinski CE, Mele F, Aschenbrenner D, Jarrossay D, Ronchi F. 162.  et al. 2012. Pathogen-induced human TH17 cells produce IFN-γ or IL-10 and are regulated by IL-1β. Nature 484:514–18 [Google Scholar]
  163. O'Garra A, Vieira P. 163.  2007. TH1 cells control themselves by producing interleukin-10. Nat. Rev. Immunol. 7:425–28 [Google Scholar]
  164. Hakulinen J, Junnikkala S, Sorsa T, Meri S. 164.  2004. Complement inhibitor membrane cofactor protein (MCP; CD46) is constitutively shed from cancer cell membranes in vesicles and converted by a metalloproteinase to a functionally active soluble form. Eur. J. Immunol. 34:2620–29 [Google Scholar]
  165. Ni Choileain S, Astier AL. 165.  2012. CD46 processing: a means of expression. Immunobiology 217:169–75 [Google Scholar]
  166. Amsen D, Helbig C, Backer RA. 166.  2015. Notch in T cell differentiation: all things considered. Trends Immunol 36:802–14 [Google Scholar]
  167. Grochowski CM, Loomes KM, Spinner NB. 167.  2016. Jagged1 (JAG1): structure, expression, and disease associations. Gene 576:381–84 [Google Scholar]
  168. Ellinghaus U, Cortini A, Pinder CL, Le Friec G, Kemper C, Vyse TJ. 168.  2017. Dysregulated CD46 shedding interferes with Th1-contraction in systemic lupus erythematosus. Eur. J. Immunol. 47:1200–10 [Google Scholar]
  169. Kemper C, Köhl J. 169.  2013. Novel roles for complement receptors in T cell regulation and beyond. Mol. Immunol. 56:181–90 [Google Scholar]
  170. Katz Y, Singer L, Wetsel RA, Schlesinger M, Fishelson Z. 170.  1994. Inherited complement C3 deficiency: a defect in C3 secretion. Eur. J. Immunol. 24:1517–22 [Google Scholar]
  171. Singer L, Whitehead WT, Akama H, Katz Y, Fishelson Z, Wetsel RA. 171.  1994. Inherited human complement C3 deficiency: An amino acid substitution in the β-chain (ASP549 to ASN) impairs C3 secretion. J. Biol. Chem. 269:28494–99 [Google Scholar]
  172. Wen H, Ting JP, O'Neill LA. 172.  2012. A role for the NLRP3 inflammasome in metabolic diseases—did Warburg miss inflammation?. Nat. Immunol. 13:352–57 [Google Scholar]
  173. Phieler J, Garcia-Martin R, Lambris JD, Chavakis T. 173.  2013. The role of the complement system in metabolic organs and metabolic diseases. Semin. Immunol. 25:47–53 [Google Scholar]
  174. Kim DD, Song WC. 174.  2006. Membrane complement regulatory proteins. Clin. Immunol. 118:127–36 [Google Scholar]
  175. Dunkelberger J, Zhou L, Miwa T, Song WC. 175.  2012. C5aR expression in a novel GFP reporter gene knockin mouse: implications for the mechanism of action of C5aR signaling in T cell immunity. J. Immunol. 188:4032–42 [Google Scholar]
  176. Ender F, Wiese AV, Schmudde I, Sun J, Vollbrandt T. 176.  et al. 2017. Differential regulation of C5a receptor 1 in innate immune cells during the allergic asthma effector phase. PLOS ONE 12:e0172446 [Google Scholar]
  177. Quell KM, Karsten CM, Kordowski A, Almeida LN, Briukhovetska D. 177.  et al. 2017. Monitoring C3aR expression using a floxed tdTomato-C3aR reporter knock-in mouse. J. Immunol. 199:688–706 [Google Scholar]
  178. Quigg RJ, Holers VM. 178.  1995. Characterization of rat complement receptors and regulatory proteins. CR2 and Crry are conserved, and the C3b receptor of neutrophils and platelets is distinct from CR1. J. Immunol. 155:1481–88 [Google Scholar]
  179. Fernández-Centeno E, de Ojeda G, Rojo JM, Portolés P. 179.  2000. Crry/p65, a membrane complement regulatory protein, has costimulatory properties on mouse T cells. J. Immunol. 164:4533–42 [Google Scholar]
  180. Hori K, Sen A, Artavanis-Tsakonas S. 180.  2013. Notch signaling at a glance. J. Cell Sci. 126:2135–40 [Google Scholar]
  181. Carmona-Fontaine C, Theveneau E, Tzekou A, Tada M, Woods M. 181.  et al. 2011. Complement fragment C3a controls mutual cell attraction during collective cell migration. Dev. Cell 21:1026–37 [Google Scholar]
  182. Rutz S, Janke M, Kassner N, Hohnstein T, Krueger M, Scheffold A. 182.  2008. Notch regulates IL-10 production by T helper 1 cells. PNAS 105:3497–502 [Google Scholar]
  183. Ciofani M, Zúñiga-Pflücker JC. 183.  2005. Notch promotes survival of pre-T cells at the β-selection checkpoint by regulating cellular metabolism. Nat. Immunol. 6:881–88 [Google Scholar]
  184. Landor SK, Mutvei AP, Mamaeva V, Jin S, Busk M. 184.  et al. 2011. Hypo- and hyperactivated Notch signaling induce a glycolytic switch through distinct mechanisms. PNAS 108:18814–19 [Google Scholar]
  185. Maekawa Y, Ishifune C, Tsukumo S, Hozumi K, Yagita H, Yasutomo K. 185.  2015. Notch controls the survival of memory CD4+ T cells by regulating glucose uptake. Nat. Med. 21:55–61 [Google Scholar]
  186. Slaninova V, Krafcikova M, Perez-Gomez R, Steffal P, Trantirek L. 186.  et al. 2016. Notch stimulates growth by direct regulation of genes involved in the control of glycolysis and the tricarboxylic acid cycle. Open Biol 6:150155 [Google Scholar]
  187. Presumey J, Bialas AR, Carroll MC. 187.  2017. Complement system in neural synapse elimination in development and disease. Adv. Immunol 135:53–79 [Google Scholar]
/content/journals/10.1146/annurev-immunol-042617-053245
Loading
Complement and the Regulation of T Cell Responses
Annual Review of Immunology 36, 309 (2018); https://doi.org/10.1146/annurev-immunol-042617-053245
/content/journals/10.1146/annurev-immunol-042617-053245
/content/journals/10.1146/annurev-immunol-042617-053245
Loading

Data & Media loading...

  • Article Type: Review Article

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error