1932
0
  1. Home
  2. A-Z Publications
  3. Annual Review of Immunology
  4. Volume 40, 2022
  5. Article

Annual Review of Immunology

Volume 40, 2022

Exposing T Cell Secrets Inside and Outside the Thymus

Abstract

I've had serious misgivings about writing this article, because from living the experience day by day, it's hard to believe my accomplishments merit the attention. To skirt this roadblock, I forced myself to pretend I was in a conversation with my trainees, trying to distill the central driving forces of my career in science. The below chronicles my evolution from would-be astronaut/ballerina to budding developmental biologist to devoted T cell immunologist. It traces my work from a focus on intrathymic events that mold developing T cells into self–major histocompatibility complex (MHC)-restricted lymphocytes to extrathymic events that fine-tune the T cell receptor (TCR) repertoire and impose the finishing touches on T cell maturation. It is a story of a few personal attributes multiplied by generous mentors, good luck, hard work, perseverance, and knowing when to step down.

Keyword(s): autobiography, recent thymic emigrants, T cell development, T cell receptor revision
Loading

Article metrics loading...

/content/journals/10.1146/annurev-immunol-101220-014126
2022-04-26
2025-02-16
Loading full text...

Full text loading...

/deliver/fulltext/immunol/40/1/annurev-immunol-101220-014126.html?itemId=/content/journals/10.1146/annurev-immunol-101220-014126&mimeType=html&fmt=ahah

Literature Cited

  1. 1. 
    Richardson JP, Fink P, Blanchard K, Macy M. 1977. Bacteria with defective rho factors suppress the effects of N mutations in bacteriophage λ. Mol. Gen. Genet. 153:81–85
     [Google Scholar]
  2. 2. 
    Bevan MJ. 1975. The major histocompatibility complex determines susceptibility to cytotoxic T cells directed against minor histocompatibility antigens. J. Exp. Med. 142:1349–64
     [Google Scholar]
  3. 3. 
    Bevan MJ. 1977. In a radiation chimera host H-2 antigens determine the immune responsiveness of donor cytotoxic cells. Nature 269:417–18
     [Google Scholar]
  4. 4. 
    Hünig T, Bevan MJ. 1981. Specificity of T-cell clones illustrates altered self hypothesis. Nature 294:460–62
     [Google Scholar]
  5. 5. 
    Fink PJ, Bevan MJ. 1978. H-2 antigens of the thymus determine lymphocyte specificity. J. Exp. Med. 148:766–75
     [Google Scholar]
  6. 6. 
    Bevan MJ, Fink PJ. 1978. The influence of thymus H-2 antigens on the specificity of maturing killer and helper cells. Immunol. Rev. 42:3–19
     [Google Scholar]
  7. 7. 
    Zinkernagel RM, Callahan GN, Klein J, Dennert G. 1978. Cytotoxic T cells learn specificity for self H-2 during differentiation in the thymus. Nature 271:251–53
     [Google Scholar]
  8. 8. 
    Fink PJ, Gallatin WM, Reichert RA, Butcher EC, Weissman IL. 1985. Homing receptor-bearing thymocytes, an immunocompetent cortical subpopulation. Nature 313:233–35
     [Google Scholar]
  9. 9. 
    Fink PJ, Bevan MJ, Weissman IL. 1984. Thymic cytotoxic T lymphocytes are primed in vivo to minor histocompatibility antigens. J. Exp. Med. 159:436–51
     [Google Scholar]
  10. 10. 
    Fink PJ, Weissman IL, Kaplan HS, Kyewski BA. 1984. The immunocompetence of murine stromal cell-associated thymocytes. J. Immunol. 133:2266–72
     [Google Scholar]
  11. 11. 
    Fink PJ, Weissman IL, Bevan MJ. 1983. Haplotype-specific suppression of cytotoxic T cell induction by antigen inappropriately presented on T cells. J. Exp. Med. 157:141–45
     [Google Scholar]
  12. 12. 
    Fink PJ, Shimonkevitz R, Bevan MJ. 1988. Veto cells. Annu. Rev. Immunol. 6:115–37
     [Google Scholar]
  13. 13. 
    Rammensee H-G, Juretic A, Nagy ZA, Klein J. 1984. Class I-restricted interaction between suppressor and cytolytic cells in the response to minor histocompatibility antigens. J. Immunol. 132:668–72
     [Google Scholar]
  14. 14. 
    Fink PJ, Rammensee H-G, Bevan MJ. 1984. Cloned cytolytic T cells can suppress primary cytotoxic responses directed against them. J. Immunol. 133:1775–81
     [Google Scholar]
  15. 15. 
    Fink PJ, Rammensee H-G, Benedetto JD, Staerz UD, Lefrancois L, Bevan MJ 1984. Studies on the mechanism of suppression of primary cytotoxic response by cloned cytotoxic T lymphocytes. J. Immunol. 133:1769–74
     [Google Scholar]
  16. 16. 
    Rammensee H-G, Fink PJ, Bevan MJ. 1984. Functional clonal deletion of class I-specific cytotoxic T lymphocytes by veto cells that express antigen. J. Immunol. 133:2390–96
     [Google Scholar]
  17. 17. 
    Hedrick SM, Cohen DI, Nielsen EA, Davis MM. 1984. Isolation of cDNA clones encoding T cell-specific membrane-associated proteins. Nature 308:149–53
     [Google Scholar]
  18. 18. 
    Davis MM, Chien YH, Gascoigne NR, Hedrick SM. 1984. A murine T cell receptor gene complex: isolation, structure and rearrangement. Immunol. Rev. 81:235–58
     [Google Scholar]
  19. 19. 
    Hedrick SM, Matis LA, Hecht TT, Samelson LE, Longo DL et al. 1982. The fine specificity of antigen and Ia determinant recognition by T cell hybridoma clones specific for pigeon cytochrome c. Cell 30:141–52
     [Google Scholar]
  20. 20. 
    Fink PJ, Matis LA, McElligott DL, Bookman M, Hedrick SM. 1986. Correlations between T cell specificity and the structure of the antigen receptor. Nature 321:219–26
     [Google Scholar]
  21. 21. 
    Sorger SB, Hedrick SM, Fink PJ, Bookman M, Matis LA. 1987. Generation of diversity in the T cell repertoire specific for pigeon cytochrome c. J. Exp. Med. 165:279–301
     [Google Scholar]
  22. 22. 
    Hedrick SM, Engel I, McElligott DL, Fink PJ, Hsu M-L et al. 1988. Selection of amino acid sequences in the beta chain of the T cell antigen receptor. Science 239:1541–44
     [Google Scholar]
  23. 23. 
    Matis LA, Sorger SB, McElligott DL, Fink PJ, Hedrick SM. 1987. The molecular basis of alloreactivity in antigen specific, major histocompatibility complex restricted T cell clones. Cell 51:59–69
     [Google Scholar]
  24. 24. 
    Fink PJ, Blair MJ, Matis LA, Hedrick SM. 1990. Molecular analysis of the influences of positive selection, tolerance induction, and antigen presentation on the T cell receptor repertoire. J. Exp. Med. 172:139–50
     [Google Scholar]
  25. 25. 
    Carbone FL, Sterry SJ, Butler J, Rodda S, Moore MW 1992. T cell receptor α-chain pairing determines the specificity of residue 262 within the Kb-restricted, ovalbumin257–264 determinant. Int. Immunol. 4:861–67
     [Google Scholar]
  26. 26. 
    Hogquist KS, Jameson SC, Heath WT, Howard JL, Bevan MJ, Carbone FR. 1994. T cell receptor antagonist peptides induce positive selection. Cell 76:17–27
     [Google Scholar]
  27. 27. 
    Dillon SR, Jameson SC, Fink PJ. 1994. Vβ5+ T cell receptors skew toward OVA + H-2Kb recognition. . J. Immunol. 152:1790–801
     [Google Scholar]
  28. 28. 
    Fink PJ, Swan K, Turk G, Moore MW, Carbone FR 1992. Both intrathymic and peripheral selection modulate the differential expression of Vβ5 among CD4+ and CD8+ T cells. J. Exp. Med. 176:1733–38
     [Google Scholar]
  29. 29. 
    Fink PJ, Fang CA, Turk GL. 1994. The induction of peripheral tolerance by the chronic activation and deletion of CD4+V beta 5+ cells. J. Immunol. 152:4270–81
     [Google Scholar]
  30. 30. 
    Blish CA, Gallay BJ, Turk G, Kline KM, Wheat W, Fink PJ. 1999. Chronic modulation of the T cell receptor repertoire in the lymphoid periphery. . J. Immunol. 162:3131–40
     [Google Scholar]
  31. 31. 
    McMahan CJ, Fink PJ. 1998. RAG reexpression and DNA recombination at T cell receptor loci in peripheral CD4+ T cells. Immunity 9:637–47
     [Google Scholar]
  32. 32. 
    Ali M, Weinreich M, Balcaitis S, Cooper CJ, Fink PJ. 2003. Differential regulation of peripheral CD4+ T cell tolerance induced by deletion and TCR revision. J. Immunol. 171:6290–96
     [Google Scholar]
  33. 33. 
    Cooper CJ, Turk GL, Sun M, Farr AG, Fink PJ. 2004. Cutting edge: TCR revision occurs in germinal centers. J. Immunol. 173:6532–36
     [Google Scholar]
  34. 34. 
    Higdon LE, Deets KA, Friesen TJ, Sze KY, Fink PJ. 2014. Receptor revision in CD4 T cells is influenced by follicular helper T cell formation and germinal center interactions. PNAS 111:5652–57
     [Google Scholar]
  35. 35. 
    Fink PJ, McMahan CJ. 2000. Lymphocytes rearrange, edit and revise their antigen receptors to be useful yet safe. Immunol. Today 21:561–66
     [Google Scholar]
  36. 36. 
    McMahan CJ, Fink PJ. 2000. Receptor revision in peripheral T cells creates a diverse Vβ repertoire. . J. Immunol. 165:6902–7
     [Google Scholar]
  37. 37. 
    Hale JS, Wubeshet M, Fink PJ. 2010. TCR revision generates functional CD4+ T cells. J. Immunol. 185:6528–34
     [Google Scholar]
  38. 38. 
    Zehn D, Bevan MJ, Fink PJ. 2007. Cutting edge: TCR revision affects predominantly Foxp3- cells and skews them toward the Th17 lineage. J. Immunol. 179:5653–57
     [Google Scholar]
  39. 39. 
    Hale JS, Ames KT, Boursalian TE, Fink PJ. 2010. Cutting edge: Rag deletion in peripheral T cells blocks TCR revision. J. Immunol. 184:5964–68
     [Google Scholar]
  40. 40. 
    Suzuki I, Fink PJ. 1998. Maximal proliferation of cytotoxic T lymphocytes requires reverse signaling through Fas ligand. J. Exp. Med. 187:123–28
     [Google Scholar]
  41. 41. 
    Suzuki I, Martin S, Boursalian TE, Beers C, Fink PJ. 2000. Fas ligand costimulates the in vivo proliferation of CD8+ T cells. J. Immunol. 165:5537–43
     [Google Scholar]
  42. 42. 
    Sun M, Ames KT, Suzuki I, Fink PJ. 2006. The cytoplasmic domain of Fas ligand costimulates TCR signals. J. Immunol. 177:1481–91
     [Google Scholar]
  43. 43. 
    Sun M, Lee S, Karray S, Levi-Strauss M, Ames KT, Fink PJ. 2007. Cutting edge: Two distinct motifs within the Fas ligand tail regulate Fas ligand-mediated costimulation. J. Immunol. 179:5639–43
     [Google Scholar]
  44. 44. 
    Sun M, Fink PJ. 2007. A new class of reverse signaling costimulators belongs to the TNF family. J. Immunol. 179:4307–12
     [Google Scholar]
  45. 45. 
    Yu W, Nagaoka H, Jankovic M, Misulovin Z, Suh H et al. 1999. Continued RAG expression in late stages of B cell development and no apparent re-induction after immunization. Nature 400:682–87
     [Google Scholar]
  46. 46. 
    Cooper CJ, Orr MT, McMahan CJ, Fink PJ. 2003. T cell receptor revision does not solely target recent thymic emigrants. J. Immunol. 171:226–33
     [Google Scholar]
  47. 47. 
    McCaughtry TM, Wilken MS, Hogquist KA. 2007. Thymic emigration revisited. J. Exp. Med. 204:2513–20
     [Google Scholar]
  48. 48. 
    Boursalian TE, Golob J, Soper DM, Cooper CJ, Fink PJ. 2004. Continued maturation of thymic emigrants in the periphery. Nat. Immunol. 5:418–25
     [Google Scholar]
  49. 49. 
    Makaroff LE, Hendricks DW, Niec RE, Fink PJ. 2009. Postthymic maturation influences the CD8 T cell response to antigen. PNAS 106:4799–804
     [Google Scholar]
  50. 50. 
    Berkley AM, Fink PJ. 2014. Cutting edge: CD8+ recent thymic emigrants exhibit increased responses to low affinity ligands and improved access to peripheral sites of inflammation. J. Immunol. 193:3262–66
     [Google Scholar]
  51. 51. 
    Friesen TJ, Ji Q, Fink PJ 2016. Recent thymic emigrants are tolerized in the absence of inflammation. J. Exp. Med. 213:913–20
     [Google Scholar]
  52. 52. 
    Hendricks DW, Fink PJ. 2011. Recent thymic emigrants are biased against the Th1 and toward the Th2 effector lineage. Blood 117:1239–49
     [Google Scholar]
  53. 53. 
    Cunningham CA, Bergsbaken T, Fink PJ. 2017. Cutting edge: Defective aerobic glycolysis defines the distinct effector function in antigen-activated CD8+ recent thymic emigrants. J. Immunol. 198:4575–80
     [Google Scholar]
  54. 54. 
    Berkley AM, Hendricks DW, Simmons KB, Fink PJ. 2013. Recent thymic emigrants and mature naïve T cells exhibit differential DNA methylation at key cytokine loci. J. Immunol. 190:6180–86
     [Google Scholar]
  55. 55. 
    Deets KA, Berkley AM, Bergsbaken T, Fink PJ. 2016. Cutting edge: Enhanced clonal burst size corrects an otherwise defective memory response by CD8+ recent thymic emigrants. J. Immunol. 196:2450–55
     [Google Scholar]
  56. 56. 
    Cunningham CA, Hoppins S, Fink PJ 2018. Cutting edge: Glycolytic metabolism and mitochondrial metabolism are uncoupled in antigen-activated CD8+ recent thymic emigrants. J. Immunol. 201:1627–32
     [Google Scholar]
  57. 57. 
    Houston EG Jr., Nechanitzky R, Fink PJ. 2008. Cutting edge: Contact with secondary lymphoid organs drives postthymic T cell maturation. J. Immunol. 181:5213–17
     [Google Scholar]
  58. 58. 
    Fink PJ, Hendricks DW. 2011. Post-thymic maturation: Young T cells assert their individuality. Nat. Rev. Immunol. 11:544–49
     [Google Scholar]
  59. 59. 
    Fink PJ. 2013. The biology of recent thymic emigrants. Annu. Rev. Immunol. 31:31–50
     [Google Scholar]
  60. 60. 
    Cunningham CA, Helm EY, Fink PJ. 2018. Reinterpreting recent thymic emigrant function: defective or adaptive?. Curr. Opin. Immunol. 51:1–6
     [Google Scholar]
  61. 61. 
    Houston EG Jr., Boursalian TE, Fink PJ. 2012. Homeostatic signals do not drive post-thymic T cell maturation. Cell. Immunol. 274:39–45
     [Google Scholar]
  62. 62. 
    Houston EG Jr., Fink PJ. 2009. MHC drives TCR repertoire shaping, but not maturation, in recent thymic emigrants. J. Immunol. 183:7244–49
     [Google Scholar]
  63. 63. 
    Marshak-Rothstein A, Fink PJ, Gridley T, Raulet DH, Bevan MJ, Gefter ML. 1979. Properties and applications of monoclonal antibodies directed against determinants of the Thy-1 locus. J. Immunol. 122:2491–97
     [Google Scholar]
/content/journals/10.1146/annurev-immunol-101220-014126
Loading
Exposing T Cell Secrets Inside and Outside the Thymus
Annual Review of Immunology 40, 1 (2022); https://doi.org/10.1146/annurev-immunol-101220-014126
/content/journals/10.1146/annurev-immunol-101220-014126
/content/journals/10.1146/annurev-immunol-101220-014126
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