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Abstract

Adaptive immune response consists of many highly regulated, multistep cascades that protect against infection while preserving the health of autologous tissue. The proper initiation, maintenance, and resolution of such responses require the precise coordination of molecular and cellular signaling over multiple time and length scales orchestrated by lymphatic transport. In order to investigate these functions and manipulate them for therapy, a comprehensive understanding of how lymphatics influence immune physiology is needed. This review presents the current mechanistic understanding of the role of the lymphatic vasculature in regulating biomolecule and cellular transport from the interstitium, peripheral tissue immune surveillance, the lymph node stroma and microvasculature, and circulating lymphocyte homing to lymph nodes. This review also discusses the ramifications of lymphatic transport in immunity as well as tolerance and concludes with examples of how lymphatic-mediated targeting of lymph nodes has been exploited for immunotherapy applications.

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2016-07-11
2024-12-05
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Literature Cited

  1. Friedlaender MH, Baer H. 1.  1972. Immunologic tolerance: role of the regional lymph node. Science 176:312–14 [Google Scholar]
  2. Friedlaender MH, Chisari FV, Baer H. 2.  1973. The role of the inflammatory response of skin and lymph nodes in the induction of sensitization to simple chemicals. J. Immunol. 111:164–70 [Google Scholar]
  3. Silberberg-Sinakin I, Thorbecke GJ, Baer RL, Rosenthal SA, Berezowsky V. 3.  1976. Antigen-bearing Langerhans cells in skin, dermal lymphatics and in lymph nodes. Cell. Immunol. 25:137–51 [Google Scholar]
  4. Thomas SN, Rutkowski JM, Pasquier M, Kuan EL, Alitalo K. 4.  et al. 2012. Impaired humoral immunity and tolerance in K14–VEGFR-3–Ig mice that lack dermal lymphatic drainage. J. Immunol. 189:2181–90Demonstrates in vivo the contribution of lymphatic transport to humoral immunity and acquired tolerance. [Google Scholar]
  5. Lund AW, Duraes FV, Hirosue S, Raghavan VR, Nembrini C. 5.  et al. 2012. VEGF-C promotes immune tolerance in B16 melanomas and cross-presentation of tumor antigen by lymph node lymphatics. Cell Rep. 1:191–99Shows that melanoma VEGF-C overexpression causes tumor- and draining lymph node–localized immune suppression despite systemic antitumor immunity. [Google Scholar]
  6. Mebius RE, Streeter PR, Brevé J, Duijvestijn AM, Kraal G. 6.  1991. The influence of afferent lymphatic vessel interruption on vascular addressin expression. J. Cell Biol. 115:85–95 [Google Scholar]
  7. Rohner NA, McClain J, Tuell SL, Warner A, Smith B. 7.  et al. 2015. Lymph node biophysical remodeling is associated with melanoma lymphatic drainage. FASEB J. 29:4512–22Demonstrates that melanoma-draining lymph nodes exhibit elevated collagen and hyaluronic acid levels and increased stiffness and viscoelasticity. [Google Scholar]
  8. Thomas SN, Vokali E, Lund AW, Hubbell JA, Swartz MA. 8.  2014. Targeting the tumor-draining lymph node with adjuvanted nanoparticles reshapes the anti-tumor immune response. Biomaterials 35:814–24Shows that tumor-draining lymph node adjuvant targeting improves the efficacy of immunotherapy. [Google Scholar]
  9. Thomas SN, Schudel A. 9.  2015. Overcoming transport barriers for interstitial-, lymphatic-, and lymph node–targeted drug delivery. Curr. Opin. Chem. Eng. 7:65–74 [Google Scholar]
  10. Jeanbart L, Ballester M, de Titta A, Corthesy P, Romero P. 10.  et al. 2014. Enhancing efficacy of anticancer vaccines by targeted delivery to tumor-draining lymph nodes. Cancer Immunol. Res. 2:436–47Shows that the efficacy of tumor vaccination is improved by targeting to lymph nodes draining solid tumors. [Google Scholar]
  11. Liu H, Moynihan KD, Zheng Y, Szeto GL, Li AV. 11.  et al. 2014. Structure-based programming of lymph-node targeting in molecular vaccines. Nature 507:519–22 [Google Scholar]
  12. Sherwood L.12.  2014. Human Physiology: From Cells to Systems San Francisco: Cengage Learning [Google Scholar]
  13. Rizwan A, Bulte C, Kalaichelvan A, Cheng M, Krishnamachary B. 13.  et al. 2015. Metastatic breast cancer cells in lymph nodes increase nodal collagen density. Sci. Rep. 5:10002 [Google Scholar]
  14. Ondondo B, Jones E, Hindley J, Cutting S, Smart K. 14.  et al. 2014. Progression of carcinogen-induced fibrosarcomas is associated with the accumulation of naive CD4+ T cells via blood vessels and lymphatics. Int. J. Cancer 134:2156–67 [Google Scholar]
  15. Negrini D, Moriondo A, Mukenge S. 15.  2004. Transmural pressure during cardiogenic oscillations in rodent diaphragmatic lymphatic vessels. Lymphat. Res. Biol. 2:69–81 [Google Scholar]
  16. Wiig H, Swartz MA. 16.  2012. Interstitial fluid and lymph formation and transport: physiological regulation and roles in inflammation and cancer. Physiol. Rev. 92:1005–60 [Google Scholar]
  17. Takahashi T, Shibata M, Kamiya A. 17.  1997. Mechanism of macromolecule concentration in collecting lymphatics in rat mesentery. Microvasc. Res. 54:193–205 [Google Scholar]
  18. Roozendaal R, Mempel TR, Pitcher LA, Gonzalez SF, Verschoor A. 18.  et al. 2009. Conduits mediate transport of low-molecular-weight antigen to lymph node follicles. Immunity 30:264–76 [Google Scholar]
  19. Junt T, Moseman EA, Iannacone M, Massberg S, Lang PA. 19.  et al. 2007. Subcapsular sinus macrophages in lymph nodes clear lymph-borne viruses and present them to antiviral B cells. Nature 450:110–14 [Google Scholar]
  20. Haessler U, Pisano M, Wu M, Swartz MA. 20.  2011. Dendritic cell chemotaxis in 3D under defined chemokine gradients reveals differential response to ligands CCL21 and CCL19. PNAS 108:5614–19 [Google Scholar]
  21. Tomura M, Hata A, Matsuoka S, Shand FH, Nakanishi Y. 21.  et al. 2014. Tracking and quantification of dendritic cell migration and antigen trafficking between the skin and lymph nodes. Sci. Rep. 4:6030 [Google Scholar]
  22. Randolph GJ, Angeli V, Swartz MA. 22.  2005. Dendritic-cell trafficking to lymph nodes through lymphatic vessels. Nat. Rev. Immunol. 5:617–28 [Google Scholar]
  23. Dubrot J, Duraes FV, Potin L, Capotosti F, Brighouse D. 23.  et al. 2014. Lymph node stromal cells acquire peptide–MHCII complexes from dendritic cells and induce antigen-specific CD4+ T cell tolerance. J. Exp. Med. 211:1153–66 [Google Scholar]
  24. Allan RS, Waithman J, Bedoui S, Jones CM, Villadangos JA. 24.  et al. 2006. Migratory dendritic cells transfer antigen to a lymph node–resident dendritic cell population for efficient CTL priming. Immunity 25:153–62 [Google Scholar]
  25. Kubo A, Nagao K, Yokouchi M, Sasaki H, Amagai M. 25.  2009. External antigen uptake by Langerhans cells with reorganization of epidermal tight junction barriers. J. Exp. Med. 206:2937–46 [Google Scholar]
  26. Clement CC, Cannizzo ES, Nastke M-D, Sahu R, Olszewski W. 26.  et al. 2010. An expanded self-antigen peptidome is carried by the human lymph as compared to the plasma. PLOS ONE 5:e9863Demonstrates that lymph is enriched in self-antigen generated by physiological tissue catabolism. [Google Scholar]
  27. Itano AA, Jenkins MK. 27.  2003. Antigen presentation to naive CD4 T cells in the lymph node. Nat. Immunol. 4:733–39 [Google Scholar]
  28. Gratz IK, Campbell DJ. 28.  2014. Organ-specific and memory treg cells: specificity, development, function, and maintenance. Front. Immunol. 5:333 [Google Scholar]
  29. Nishikawa H, Sakaguchi S. 29.  2014. Regulatory T cells in cancer immunotherapy. Curr. Opin. Immunol. 27:1–7 [Google Scholar]
  30. Hubbell JA, Thomas SN, Swartz MA. 30.  2009. Materials engineering for immunomodulation. Nature 462:449–60 [Google Scholar]
  31. Olszewski WL, Pazdur J, Kubasiewicz E, Zaleska M, Cooke CJ, Miller NE. 31.  2001. Lymph draining from foot joints in rheumatoid arthritis provides insight into local cytokine and chemokine production and transport to lymph nodes. Arthritis Rheum. 44:541–49Shows that lymph-draining joints of rheumatoid arthritis patients is highly enriched in immunomodulatory cytokines and chemokines. [Google Scholar]
  32. Robbins PD, Morelli AE. 32.  2014. Regulation of immune responses by extracellular vesicles. Nat. Rev. Immunol. 14:195–208 [Google Scholar]
  33. Hood JL, San RS, Wickline SA. 33.  2011. Exosomes released by melanoma cells prepare sentinel lymph nodes for tumor metastasis. Cancer Res. 71:3792–801 [Google Scholar]
  34. Kunder CA, St John AL, Li G, Leong KW, Berwin B. 34.  et al. 2009. Mast cell–derived particles deliver peripheral signals to remote lymph nodes. J. Exp. Med. 206:2455–67 [Google Scholar]
  35. Davalos-Misslitz AC, Rieckenberg J, Willenzon S, Worbs T, Kremmer E. 35.  et al. 2007. Generalized multi-organ autoimmunity in CCR7-deficient mice. Eur. J. Immunol. 37:613–22 [Google Scholar]
  36. Mueller SN, Germain RN. 36.  2009. Stromal cell contributions to the homeostasis and functionality of the immune system. Nat. Rev. Immunol. 9:618–29 [Google Scholar]
  37. Drayton DL, Liao S, Mounzer RH, Ruddle NH. 37.  2006. Lymphoid organ development: from ontogeny to neogenesis. Nat. Immunol. 7:344–53 [Google Scholar]
  38. Bajenoff M, Egen JG, Koo LY, Laugier JP, Brau F. 38.  et al. 2006. Stromal cell networks regulate lymphocyte entry, migration, and territoriality in lymph nodes. Immunity 25:989–1001 [Google Scholar]
  39. Tomei AA, Siegert S, Britschgi MR, Luther SA, Swartz MA. 39.  2009. Fluid flow regulates stromal cell organization and CCL21 expression in a tissue-engineered lymph node microenvironment. J. Immunol. 183:4273–83 [Google Scholar]
  40. Halin C, Tobler NE, Vigl B, Brown LF, Detmar M. 40.  2007. VEGF-A produced by chronically inflamed tissue induces lymphangiogenesis in draining lymph nodes. Blood 110:3158–67 [Google Scholar]
  41. Acton SE, Farrugia AJ, Astarita JL, Mourão-Sá D, Jenkins RP. 41.  et al. 2014. Dendritic cells control fibroblastic reticular network tension and lymph node expansion. Nature 514:498–502 [Google Scholar]
  42. Martín-Fontecha A, Sebastiani S, Höpken UE, Uguccioni M, Lipp M. 42.  et al. 2003. Regulation of dendritic cell migration to the draining lymph node: impact on T lymphocyte traffic and priming. J. Exp. Med. 198:615–21 [Google Scholar]
  43. Webster B, Ekland EH, Agle LM, Chyou S, Ruggieri R, Lu TT. 43.  2006. Regulation of lymph node vascular growth by dendritic cells. J. Exp. Med. 203:1903–13 [Google Scholar]
  44. Paszek MJ, Zahir N, Johnson KR, Lakins JN, Rozenberg GI. 44.  et al. 2005. Tensional homeostasis and the malignant phenotype. Cancer Cell 8:241–54 [Google Scholar]
  45. Shields JD, Fleury ME, Yong C, Tomei AA, Randolph GJ, Swartz MA. 45.  2007. Autologous chemotaxis as a mechanism of tumor cell homing to lymphatics via interstitial flow and autocrine CCR7 signaling. Cancer Cell 11:526–38 [Google Scholar]
  46. Shieh AC, Rozansky HA, Hinz B, Swartz MA. 46.  2011. Tumor cell invasion is promoted by interstitial flow–induced matrix priming by stromal fibroblasts. Cancer Res. 71:790–800 [Google Scholar]
  47. Barcus CE, Keely PJ, Eliceiri KW, Schuler LA. 47.  2013. Stiff collagen matrices increase tumorigenic prolactin signaling in breast cancer cells. J. Biol. Chem. 288:12722–32 [Google Scholar]
  48. Insana MF, Pellot-Barakat C, Sridhar M, Lindfors KK. 48.  2004. Viscoelastic imaging of breast tumor microenvironment with ultrasound. J. Mammary Gland Biol. Neoplasia 9:393–404 [Google Scholar]
  49. Gutmann R, Leunig M, Feyh J, Goetz AE, Messmer K. 49.  et al. 1992. Interstitial hypertension in head and neck tumors in patients: correlation with tumor size. Cancer Res. 52:1993–95 [Google Scholar]
  50. Nathanson SD, Mahan M. 50.  2011. Sentinel lymph node pressure in breast cancer. Ann. Surg. Oncol. 18:3791–96 [Google Scholar]
  51. Nathanson SD, Shah R, Chitale DA, Mahan M. 51.  2014. Intraoperative clinical assessment and pressure measurements of sentinel lymph nodes in breast cancer. Ann. Surg. Oncol. 21:81–85 [Google Scholar]
  52. O'Connor RS, Hao X, Shen K, Bashour K, Akimova T. 52.  et al. 2012. Substrate rigidity regulates human T cell activation and proliferation. J. Immunol. 189:1330–39 [Google Scholar]
  53. Abreu EL, Palmer MP, Murray MM. 53.  2010. Collagen density significantly affects the functional properties of an engineered provisional scaffold. J. Biomed. Mater. Res. A 93:150–57 [Google Scholar]
  54. Chang S-F, Chang CA, Lee D-Y, Lee P-L, Yeh Y-M. 54.  et al. 2008. Tumor cell cycle arrest induced by shear stress: roles of integrins and Smad. PNAS 105:3927–32 [Google Scholar]
  55. Vincent T, Jourdan M, Sy MS, Klein B, Mechti N. 55.  2001. Hyaluronic acid induces survival and proliferation of human myeloma cells through an interleukin-6-mediated pathway involving the phosphorylation of retinoblastoma protein. J. Biol. Chem. 276:14728–36 [Google Scholar]
  56. Rafi A, Nagarkatti M, Nagarkatti PS. 56.  1997. Hyaluronate–CD44 interactions can induce murine B-cell activation. Blood 89:2901–8 [Google Scholar]
  57. Tan Y, Tajik A, Chen J, Jia Q, Chowdhury F. 57.  et al. 2014. Matrix softness regulates plasticity of tumour-repopulating cells via H3K9 demethylation and Sox2 expression. Nat. Commun. 5:4619 [Google Scholar]
  58. Tilghman RW, Cowan CR, Mih JD, Koryakina Y, Gioeli D. 58.  et al. 2010. Matrix rigidity regulates cancer cell growth and cellular phenotype. PLOS ONE 5:e12905 [Google Scholar]
  59. Hind LE, Dembo M, Hammer DA. 59.  2015. Macrophage motility is driven by frontal-towing with a force magnitude dependent on substrate stiffness. Integr. Biol. Quant. Biosci. Nano Macro 7:447–53 [Google Scholar]
  60. Oakes PW, Patel DC, Morin NA, Zitterbart DP, Fabry B. 60.  et al. 2009. Neutrophil morphology and migration are affected by substrate elasticity. Blood 114:1387–95 [Google Scholar]
  61. Miron-Mendoza M, Seemann J, Grinnell F. 61.  2010. The differential regulation of cell motile activity through matrix stiffness and porosity in three dimensional collagen matrices. Biomaterials 31:6425–35 [Google Scholar]
  62. Huang JH, Cárdenas-Navia LI, Caldwell CC, Plumb TJ, Radu CG. 62.  et al. 2007. Requirements for T lymphocyte migration in explanted lymph nodes. J. Immunol. 178:7747–55 [Google Scholar]
  63. Kaiser A, Donnadieu E, Abastado JP, Trautmann A, Nardin A. 63.  2005. CC chemokine ligand 19 secreted by mature dendritic cells increases naive T cell scanning behavior and their response to rare cognate antigen. J. Immunol. 175:2349–56 [Google Scholar]
  64. Haessler U, Pisano M, Wu M, Swartz MA. 64.  2011. Dendritic cell chemotaxis in 3D under defined chemokine gradients reveals differential response to ligands CCL21 and CCL19. PNAS 108:5614–19 [Google Scholar]
  65. Polacheck WJ, Charest JL, Kamm RD. 65.  2011. Interstitial flow influences direction of tumor cell migration through competing mechanisms. PNAS 108:11115–20 [Google Scholar]
  66. Shi ZD, Ji XY, Qazi H, Tarbell JM. 66.  2009. Interstitial flow promotes vascular fibroblast, myofibroblast, and smooth muscle cell motility in 3-D collagen I via upregulation of MMP-1. Am. J. Physiol. Heart Circ. Physiol. 297:H1225–34 [Google Scholar]
  67. Galimberti M, Tolić-Nørrelykke IM, Favillini R, Mercatelli R, Annunziato F. 67.  et al. 2006. Hypergravity speeds up the development of T-lymphocyte motility. Eur. Biophys. J. 35:393–400 [Google Scholar]
  68. Tien J, Truslow JG, Nelson CM. 68.  2012. Modulation of invasive phenotype by interstitial pressure-driven convection in aggregates of human breast cancer cells. PLOS ONE 7e45191 [Google Scholar]
  69. von Andrian UH, Mempel TR. 69.  2003. Homing and cellular traffic in lymph nodes. Nat. Rev. Immunol. 3:867–78 [Google Scholar]
  70. Marchesi VT, Gowans JL. 70.  1964. The migration of lymphocytes through the endothelium of venules in lymph nodes: an electron microscope study. Proc. R. Soc. B 159:283–90 [Google Scholar]
  71. Arbones ML, Ord DC, Ley K, Ratech H, Maynard-Curry C. 71.  et al. 1994. Lymphocyte homing and leukocyte rolling and migration are impaired in L-selectin-deficient mice. Immunity 1:247–60 [Google Scholar]
  72. Kansas GS, Ley K, Munro JM, Tedder TF. 72.  1993. Regulation of leukocyte rolling and adhesion to high endothelial venules through the cytoplasmic domain of L-selectin. J. Exp. Med. 177:833–38 [Google Scholar]
  73. Subramanian H, Grailer JJ, Ohlrich KC, Rymaszewski AL, Loppnow JJ. 73.  et al. 2012. Signaling through L-selectin mediates enhanced chemotaxis of lymphocyte subsets to secondary lymphoid tissue chemokine. J. Immunol. 188:3223–36 [Google Scholar]
  74. Mebius RE, Streeter PR, Brevé J, Duijvestijn AM, Kraal G. 74.  1991. The influence of afferent lymphatic vessel interruption on vascular addressin expression. J. Cell Biol. 115:85–95 [Google Scholar]
  75. Diacovo TG, Puri KD, Warnock RA, Springer TA, von Andrian UH. 75.  1996. Platelet-mediated lymphocyte delivery to high endothelial venules. Science 273:252–55 [Google Scholar]
  76. Bargatze RF, Jutila MA, Butcher EC. 76.  1995. Distinct roles of L-selectin and integrins α4β7 and LFA-1 in lymphocyte homing to Peyer's patch–HEV in situ: the multistep model confirmed and refined. Immunity 3:99–108 [Google Scholar]
  77. Mebius RE, Streeter PR, Michie S, Butcher EC, Weissman IL. 77.  1996. A developmental switch in lymphocyte homing receptor and endothelial vascular addressin expression regulates lymphocyte homing and permits CD4+ CD3 cells to colonize lymph nodes. PNAS 93:11019–24 [Google Scholar]
  78. Boscacci RT, Pfeiffer F, Gollmer K, Sevilla AI, Martin AM. 78.  et al. 2010. Comprehensive analysis of lymph node stroma–expressed Ig superfamily members reveals redundant and nonredundant roles for ICAM-1, ICAM-2, and VCAM-1 in lymphocyte homing. Blood 116:915–25 [Google Scholar]
  79. Stein JV, Rot A, Luo Y, Narasimhaswamy M, Nakano H. 79.  et al. 2000. The CC chemokine thymus–derived chemotactic agent 4 (TCA-4, secondary lymphoid tissue chemokine, 6ckine, exodus-2) triggers lymphocyte function–associated antigen 1–mediated arrest of rolling T lymphocytes in peripheral lymph node high endothelial venules. J. Exp. Med. 191:61–76 [Google Scholar]
  80. Okada T, Ngo VN, Ekland EH, Förster R, Lipp M. 80.  et al. 2002. Chemokine requirements for B cell entry to lymph nodes and Peyer's patches. J. Exp. Med. 196:65–75 [Google Scholar]
  81. Baekkevold ES, Yamanaka T, Palframan RT, Carlsen HS, Reinholt FP. 81.  et al. 2001. The CCR7 ligand ELC (CCL19) is transcytosed in high endothelial venules and mediates T cell recruitment. J. Exp. Med. 193:1105–12 [Google Scholar]
  82. Shamri R, Grabovsky V, Gauguet J-M, Feigelson S, Manevich E. 82.  et al. 2005. Lymphocyte arrest requires instantaneous induction of an extended LFA-1 conformation mediated by endothelium-bound chemokines. Nat. Immunol. 6:497–506 [Google Scholar]
  83. Chen Q, Fisher DT, Clancy KA, Gauguet J-MM, Wang W-C. 83.  et al. 2006. Fever-range thermal stress promotes lymphocyte trafficking across high endothelial venules via an interleukin 6 trans-signaling mechanism. Nat. Immunol. 7:1299–308 [Google Scholar]
  84. Roozendaal R, Mebius RE, Kraal G. 84.  2008. The conduit system of the lymph node. Int. Immunol. 20:1483–87 [Google Scholar]
  85. Gretz JE, Norbury CC, Anderson AO, Proudfoot AE, Shaw S. 85.  2000. Lymph-borne chemokines and other low molecular weight molecules reach high endothelial venules via specialized conduits while a functional barrier limits access to the lymphocyte microenvironments in lymph node cortex. J. Exp. Med. 192:1425–40Demonstrates a transport role of lymph node conduits and their molecular size-dependent profiles of exclusion. [Google Scholar]
  86. Lu TT, Browning JL. 86.  2014. Role of the lymphotoxin/LIGHT system in the development and maintenance of reticular networks and vasculature in lymphoid tissues. Front. Immunol. 5:47 [Google Scholar]
  87. Palframan RT, Jung S, Cheng G, Weninger W, Luo Y. 87.  et al. 2001. Inflammatory chemokine transport and presentation in HEV: a remote control mechanism for monocyte recruitment to lymph nodes in inflamed tissues. J. Exp. Med. 194:1361–74 [Google Scholar]
  88. Kumar V, Chyou S, Stein JV, Lu TT. 88.  2012. Optical projection tomography reveals dynamics of HEV growth after immunization with protein plus CFA and features shared with HEVs in acute autoinflammatory lymphadenopathy. Front. Immunol. 3:282 [Google Scholar]
  89. Kumar V, Scandella E, Danuser R, Onder L, Nitschké M. 89.  et al. 2010. Global lymphoid tissue remodeling during a viral infection is orchestrated by a B cell–lymphotoxin-dependent pathway. Blood 115:4725–33 [Google Scholar]
  90. Liao S, Ruddle NH. 90.  2006. Synchrony of high endothelial venules and lymphatic vessels revealed by immunization. J. Immunol. 177:3369–79 [Google Scholar]
  91. Shrestha B, Hashiguchi T, Ito T, Miura N, Takenouchi K. 91.  et al. 2010. B cell–derived vascular endothelial growth factor A promotes lymphangiogenesis and high endothelial venule expansion in lymph nodes. J. Immunol. 184:4819–26 [Google Scholar]
  92. Chyou S, Benahmed F, Chen J, Kumar V, Tian S. 92.  et al. 2011. Coordinated regulation of lymph node vascular–stromal growth first by CD11c+ cells and then by T and B cells. J. Immunol. 187:5558–67 [Google Scholar]
  93. Tong Z, Cheung LS-L, Stebe KJ, Konstantopoulos K. 93.  2012. Selectin-mediated adhesion in shear flow using micropatterned substrates: Multiple-bond interactions govern the critical length for cell binding. Integr. Biol. 4:847–56 [Google Scholar]
  94. Atarashi K, Hirata T, Matsumoto M, Kanemitsu N, Miyasaka M. 94.  2005. Rolling of Th1 cells via P-selectin glycoprotein ligand 1 stimulates LFA-1-mediated cell binding to ICAM-1. J. Immunol. 174:1424–32 [Google Scholar]
  95. Oh J, Edwards EE, McClatchey PM, Thomas SN. 95.  2015. Analytical cell adhesion chromatography reveals impaired persistence of metastatic cell rolling adhesion to P-selectin. J. Cell Sci. 128:3731–43Shows that the persistence of selectin-mediated rolling adhesion is cell subtype dependent. [Google Scholar]
  96. Papaioannou TG, Stefanadis C. 96.  2005. Vascular wall shear stress: basic principles and methods. Hell. J. Cardiol. 46:9–15 [Google Scholar]
  97. Finger EB, Puri KD, Alon R, Lawrence MB, von Andrian UH, Springer TA. 97.  1996. Adhesion through L-selectin requires a threshold hydrodynamic shear. Nature 379:266–69 [Google Scholar]
  98. Woolf E, Grigorova I, Sagiv A, Grabovsky V, Feigelson SW. 98.  et al. 2007. Lymph node chemokines promote sustained T lymphocyte motility without triggering stable integrin adhesiveness in the absence of shear forces. Nat. Immunol. 8:1076–85 [Google Scholar]
  99. Tewalt EF, Cohen JN, Rouhani SJ, Guidi CJ, Qiao H. 99.  et al. 2012. Lymphatic endothelial cells induce tolerance via PD-L1 and lack of costimulation leading to high-level PD-1 expression on CD8 T cells. Blood 120:4772–82 [Google Scholar]
  100. Rouhani SJ, Eccles JD, Riccardi P, Peske JD, Tewalt EF. 100.  et al. 2015. Roles of lymphatic endothelial cells expressing peripheral tissue antigens in CD4 T-cell tolerance induction. Nat. Commun. 6:6771 [Google Scholar]
  101. Hirosue S, Vokali E, Raghavan VR, Rincon-Restrepo M, Lund AW. 101.  et al. 2014. Steady-state antigen scavenging, cross-presentation, and CD8+ T cell priming: a new role for lymphatic endothelial cells. J. Immunol. 192:5002–11 [Google Scholar]
  102. Swartz MA.102.  2014. Immunomodulatory roles of lymphatic vessels in cancer progression. Cancer Immunol. Res. 2:701–7 [Google Scholar]
  103. Fletcher AL, Malhotra D, Turley SJ. 103.  2011. Lymph node stroma broaden the peripheral tolerance paradigm. Trends Immunol. 32:12–18 [Google Scholar]
  104. Card CM, Yu SS, Swartz MA. 104.  2014. Emerging roles of lymphatic endothelium in regulating adaptive immunity. J. Clin. Investig. 124:943–52 [Google Scholar]
  105. Hirosue S, Dubrot J. 105.  2015. Modes of antigen presentation by lymph node stromal cells and their immunological implications. Front. Immunol 6:446 [Google Scholar]
  106. Tamburini BA, Burchill MA, Kedl RM. 106.  2014. Antigen capture and archiving by lymphatic endothelial cells following vaccination or viral infection. Nat. Commun. 5:3989 [Google Scholar]
  107. Ridner SH.107.  2013. Pathophysiology of lymphedema. Semin. Oncol. Nurs. 29:4–11 [Google Scholar]
  108. Rutkowski JM, Markhus CE, Gyenge CC, Alitalo K, Wiig H, Swartz MA. 108.  2010. Dermal collagen and lipid deposition correlate with tissue swelling and hydraulic conductivity in murine primary lymphedema. Am. J. Pathol. 176:1122–29 [Google Scholar]
  109. Ghanta S, Cuzzone DA, Torrisi JS, Albano NJ, Joseph WJ. 109.  et al. 2015. Regulation of inflammation and fibrosis by macrophages in lymphedema. Am. J. Physiol. Heart Circ. Physiol. 308:H1065–77 [Google Scholar]
  110. Baird JB, Charles JL, Streit TG, Roberts JM, Addiss DG, Lammie PJ. 110.  2002. Reactivity to bacterial, fungal, and parasite antigens in patients with lymphedema and elephantiasis. Am. J. Trop. Med. Hyg. 66:163–69 [Google Scholar]
  111. Rossy K.111.  2013. Lymphedema. Medscape Jan. 8. http://emedicine.medscape.com/article/1087313-overview [Google Scholar]
  112. Carlson JA.112.  2014. Lymphedema and subclinical lymphostasis (microlymphedema) facilitate cutaneous infection, inflammatory dermatoses, and neoplasia: a locus minoris resistentiae. Clin. Dermatol. 32:599–615 [Google Scholar]
  113. Bordea C, Wojnarowska F, Morris PJ. 113.  1999. Multiple cutaneous malignancies arising in limbs with signs of lymphatic insufficiency in transplant patients. Br. J. Plast. Surg. 52:619–22 [Google Scholar]
  114. Mallon E, Powell S, Mortimer P, Ryan TJ. 114.  1997. Evidence for altered cell-mediated immunity in postmastectomy lymphoedema. Br. J. Dermatol. 137:928–33 [Google Scholar]
  115. Stark RB, Dwyer EM, Deforest M. 115.  1960. Effect of surgical ablation of regional lymph nodes on survival of skin homografts. Ann. N. Y. Acad. Sci. 87:140–48 [Google Scholar]
  116. Lambert PB, Frank HA, Bellman S, Farnsworth D. 116.  1965. The role of the lymph trunks in the response to allogeneic skin transplants. Transplantation 3:62–73 [Google Scholar]
  117. Yin N, Zhang N, Xu J, Shi Q, Ding Y, Bromberg JS. 117.  2011. Targeting lymphangiogenesis after islet transplantation prolongs islet allograft survival. Transplantation 92:25–30 [Google Scholar]
  118. Albuquerque RJ, Hayashi T, Cho WG, Kleinman ME, Dridi S. 118.  et al. 2009. Alternatively spliced vascular endothelial growth factor receptor 2 is an essential endogenous inhibitor of lymphatic vessel growth. Nat. Med. 15:1023–30 [Google Scholar]
  119. Kerjaschki D, Regele HM, Moosberger I, Nagy-Bojarski K, Watschinger B. 119.  et al. 2004. Lymphatic neoangiogenesis in human kidney transplants is associated with immunologically active lymphocytic infiltrates. J. Am. Soc. Nephrol. 15:603–12 [Google Scholar]
  120. Mori S, Nakano H, Aritomi K, Wang CR, Gunn MD, Kakiuchi T. 120.  2001. Mice lacking expression of the chemokines Ccl21-ser and Ccl19 (plt mice) demonstrate delayed but enhanced T cell immune responses. J. Exp. Med. 193:207–18 [Google Scholar]
  121. Teoh D, Johnson LA, Hanke T, McMichael AJ, Jackson DG. 121.  2009. Blocking development of a CD8+ T cell response by targeting lymphatic recruitment of APC. J. Immunol. 182:2425–31 [Google Scholar]
  122. Hofmann J, Greter M, Du Pasquier L, Becher B. 122.  2010. B cells need a proper house, whereas T cells are happy in a cave: the dependence of lymphocytes on secondary lymphoid tissues during evolution. Trends Immunol. 31:144–53 [Google Scholar]
  123. Shinkura R, Kitada K, Matsuda F, Tashiro K, Ikuta K. 123.  et al. 1999. Alymphoplasia is caused by a point mutation in the mouse gene encoding NF-κB-inducing kinase. Nat. Genet. 22:74–77 [Google Scholar]
  124. Greter M, Hofmann J, Becher B. 124.  2009. Neo-lymphoid aggregates in the adult liver can initiate potent cell-mediated immunity. PLOS Biol. 7:e1000109 [Google Scholar]
  125. Mäkinen T, Veikkola T, Mustjoki S, Karpanen T, Catimel B. 125.  et al. 2001. Isolated lymphatic endothelial cells transduce growth, survival and migratory signals via the VEGF-C/D receptor VEGFR-3. EMBO J. 20:4762–73 [Google Scholar]
  126. MacLennan IC.126.  1994. Germinal centers. Annu. Rev. Immunol. 12:117–39 [Google Scholar]
  127. Watanabe R, Fujimoto M, Ishiura N, Kuwano Y, Nakashima H. 127.  et al. 2007. CD19 expression in B cells is important for suppression of contact hypersensitivity. Am. J. Pathol. 171:560–70 [Google Scholar]
  128. Förster R, Davalos-Misslitz AC, Rot A. 128.  2008. CCR7 and its ligands: balancing immunity and tolerance. Nat. Rev. Immunol. 8:362–71 [Google Scholar]
  129. Saito E, Fujimoto M, Hasegawa M, Komura K, Hamaguchi Y. 129.  et al. 2002. CD19-dependent B lymphocyte signaling thresholds influence skin fibrosis and autoimmunity in the tight-skin mouse. J. Clin. Investig. 109:1453–62 [Google Scholar]
  130. Sato S, Hasegawa M, Fujimoto M, Tedder TF, Takehara K. 130.  2000. Quantitative genetic variation in CD19 expression correlates with autoimmunity. J. Immunol. 165:6635–43 [Google Scholar]
  131. Wengner AM, Höpken UE, Petrow PK, Hartmann S, Schurigt U. 131.  et al. 2007. CXCR5- and CCR7-dependent lymphoid neogenesis in a murine model of chronic antigen-induced arthritis. Arthritis Rheum. 56:3271–83 [Google Scholar]
  132. Harrell MI, Iritani BM, Ruddell A. 132.  2007. Tumor-induced sentinel lymph node lymphangiogenesis and increased lymph flow precede melanoma metastasis. Am. J. Pathol. 170:774–86 [Google Scholar]
  133. Schudel A, Kassis T, Dixon JB, Thomas SN. 133.  2015. S-Nitrosated polypropylene sulfide nanoparticles for thiol-dependent transnitrosation and toxicity against adult female filarial worms. Adv. Healthc. Mater. 4:1484–90 [Google Scholar]
  134. Hanson MC, Crespo MP, Abraham W, Moynihan KD, Szeto GL. 134.  et al. 2015. Nanoparticulate STING agonists are potent lymph node–targeted vaccine adjuvants. J. Clin. Investig. 125:2532–46 [Google Scholar]
  135. Li AV, Moon JJ, Abraham W, Suh H, Elkhader J. 135.  et al. 2013. Generation of effector memory T cell–based mucosal and systemic immunity with pulmonary nanoparticle vaccination. Sci. Transl. Med. 5:204ra130 [Google Scholar]
  136. Dane KY, Nembrini C, Tomei AA, Eby JK, O'Neil CP. 136.  et al. 2011. Nano-sized drug-loaded micelles deliver payload to lymph node immune cells and prolong allograft survival. J. Control. Release 156:154–60 [Google Scholar]
  137. Pujol-Autonell I, Serracant-Prat A, Cano-Sarabia M, Ampudia RM, Rodriguez-Fernandez S. 137.  et al. 2015. Use of autoantigen-loaded phosphatidylserine-liposomes to arrest autoimmunity in type 1 diabetes. PLOS ONE 10:e0127057 [Google Scholar]
  138. Nembrini C, Stano A, Dane KY, Ballester M, van der Vlies AJ. 138.  et al. 2011. Nanoparticle conjugation of antigen enhances cytotoxic T cell responses in pulmonary vaccination. PNAS 108:e989–97 [Google Scholar]
  139. Ballester M, Nembrini C, Dhar N, de Titta A, de Piano C. 139.  et al. 2011. Nanoparticle conjugation and pulmonary delivery enhance the protective efficacy of Ag85B and CpG against tuberculosis. Vaccine 29:6959–66 [Google Scholar]
  140. Tefany FJ, Barnetson RS, Halliday GM, McCarthy SW, McCarthy WH. 140.  1991. Immunocytochemical analysis of the cellular infiltrate in primary regressing and non-regressing malignant melanoma. J. Investig. Dermatol. 97:197–202 [Google Scholar]
  141. Baitsch L, Baumgaertner P, Devêvre E, Raghav SK, Legat A. 141.  et al. 2011. Exhaustion of tumor-specific CD8+ T cells in metastases from melanoma patients. J. Clin. Investig. 121:2350–60 [Google Scholar]
  142. Cochran AJ, Morton DL, Stern S, Lana AM, Essner R, Wen DR. 142.  2001. Sentinel lymph nodes show profound downregulation of antigen-presenting cells of the paracortex: implications for tumor biology and treatment. Mod. Pathol. 14:604–8 [Google Scholar]
  143. Pinzon-Charry A, Maxwell T, López JA. 143.  2005. Dendritic cell dysfunction in cancer: a mechanism for immunosuppression. Immunol. Cell Biol. 83:451–61 [Google Scholar]
  144. Yamshchikov GV, Barnd DL, Eastham S, Galavotti H, Patterson JW. 144.  et al. 2001. Evaluation of peptide vaccine immunogenicity in draining lymph nodes and peripheral blood of melanoma patients. Int. J. Cancer 92:703–11 [Google Scholar]
  145. Banchereau J, Palucka AK, Dhodapkar M, Burkeholder S, Taquet N. 145.  et al. 2001. Immune and clinical responses in patients with metastatic melanoma to CD34+ progenitor–derived dendritic cell vaccine. Cancer Res. 61:6451–58 [Google Scholar]
  146. Romero P, Dunbar PR, Valmori D, Pittet M, Ogg GS. 146.  et al. 1998. Ex vivo staining of metastatic lymph nodes by class I major histocompatibility complex tetramers reveals high numbers of antigen-experienced tumor-specific cytolytic T lymphocytes. J. Exp. Med. 188:1641–50 [Google Scholar]
  147. Jarmalavicius S, Welte Y, Walden P. 147.  2012. High immunogenicity of the human leukocyte antigen peptidomes of melanoma tumor cells. J. Biol. Chem. 287:33401–11 [Google Scholar]
  148. Mohos A, Sebestyén T, Liszkay G, Plótár V, Horváth S. 148.  et al. 2013. Immune cell profile of sentinel lymph nodes in patients with malignant melanoma—FOXP3+ cell density in cases with positive sentinel node status is associated with unfavorable clinical outcome. J. Transl. Med. 11:43 [Google Scholar]
  149. Klinman DM.149.  2004. Immunotherapeutic uses of CpG oligodeoxynucleotides. Nat. Rev. Immunol. 4:249–58 [Google Scholar]
  150. Reddy ST, Rehor A, Schmoekel HG, Hubbell JA, Swartz MA. 150.  2006. In vivo targeting of dendritic cells in lymph nodes with poly(propylene sulfide) nanoparticles. J. Control. Release 112:26–34 [Google Scholar]
  151. Kourtis IC, Hirosue S, de Titta A, Kontos S, Stegmann T. 151.  et al. 2013. Peripherally administered nanoparticles target monocytic myeloid cells, secondary lymphoid organs and tumors in mice. PLOS ONE 8:e61646 [Google Scholar]
  152. Coates PT, Colvin BL, Hackstein H, Thomson AW. 152.  2002. Manipulation of dendritic cells as an approach to improved outcomes in transplantation. Expert Rev. Mol. Med. 4:1–21 [Google Scholar]
  153. Ehser S, Chuang JJ, Kleist C, Sandra-Petrescu F, Iancu M. 153.  et al. 2008. Suppressive dendritic cells as a tool for controlling allograft rejection in organ transplantation: promises and difficulties. Hum. Immunol. 69:165–73 [Google Scholar]
  154. Komori J, Boone L, DeWard A, Hoppo T, Lagasse E. 154.  2012. The mouse lymph node as an ectopic transplantation site for multiple tissues. Nat. Biotechnol. 30:976–83 [Google Scholar]
  155. Ploix C, Bergerot I, Fabien N, Perche S, Moulin V, Thivolet C. 155.  1998. Protection against autoimmune diabetes with oral insulin is associated with the presence of IL-4 type 2 T cells in the pancreas and pancreatic lymph nodes. Diabetes 47:39–44 [Google Scholar]
  156. Tian B, Hao J, Zhang Y, Tian L, Yi H. 156.  et al. 2009. Upregulating CD4+CD25+FOXP3+ regulatory T cells in pancreatic lymph nodes in diabetic NOD mice by adjuvant immunotherapy. Transplantation 87:198–206 [Google Scholar]
  157. Trepel M, Arap W, Pasqualini R. 157.  2001. Modulation of the immune response by systemic targeting of antigens to lymph nodes. Cancer Res. 61:8110–12 [Google Scholar]
  158. Jewell CM, Lopez SC, Irvine DJ. 158.  2011. In situ engineering of the lymph node microenvironment via intranodal injection of adjuvant-releasing polymer particles. PNAS 108:15745–50 [Google Scholar]
  159. Mueller SN, Tian S, DeSimone JM. 159.  2015. Rapid and persistent delivery of antigen by lymph node targeting PRINT nanoparticle vaccine carrier to promote humoral immunity. Mol. Pharm. 12:1356–65 [Google Scholar]
  160. Eby JK, Dane KY, O'Neil CP, Hirosue S, Swartz MA, Hubbell JA. 160.  2012. Polymer micelles with pyridyl disulfide–coupled antigen travel through lymphatics and show enhanced cellular responses following immunization. Acta Biomater. 8:3210–17 [Google Scholar]
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