IMMUNE NETWORK

  • 제23권1호
  • /
  • Pages.2.1-2.19
  • /
  • 2023
  • /
  • 1598-2629(pISSN)
  • /
  • 2092-6685(eISSN)
대한면역학회 (The Korean Association of Immunobiologists)
권호 표지
DOI QR코드

DOI QR Code

Shaping Heterogeneity of Naive CD8+ T Cell Pools

  • Sung-Woo Lee (Medical Research Center for Combinatorial Tumor Immunotherapy, Department of Microbiology and Immunology, Chonnam National University Medical School) ;
  • Gil-Woo Lee (Medical Research Center for Combinatorial Tumor Immunotherapy, Department of Microbiology and Immunology, Chonnam National University Medical School) ;
  • Hee-Ok Kim (Selecxine Inc.) ;
  • Jae-Ho Cho (Medical Research Center for Combinatorial Tumor Immunotherapy, Department of Microbiology and Immunology, Chonnam National University Medical School)
  • 투고 : 2022.12.30
  • 심사 : 2023.02.12
  • 발행 : 2023.02.28
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Immune diversification helps protect the host against a myriad of pathogens. CD8+ T cells are essential adaptive immune cells that inhibit the spread of pathogens by inducing apoptosis in infected host cells, ultimately ensuring complete elimination of infectious pathogens and suppressing disease development. Accordingly, numerous studies have been conducted to elucidate the mechanisms underlying CD8+ T cell activation, proliferation, and differentiation into effector and memory cells, and to identify various intrinsic and extrinsic factors regulating these processes. The current knowledge accumulated through these studies has led to a huge breakthrough in understanding the existence of heterogeneity in CD8+ T cell populations during immune response and the principles underlying this heterogeneity. As the heterogeneity in effector/memory phases has been extensively reviewed elsewhere, in the current review, we focus on CD8+ T cells in a "naive" state, introducing recent studies dealing with the heterogeneity of naive CD8+ T cells and discussing the factors that contribute to such heterogeneity. We also discuss how this heterogeneity contributes to establishing the immense complexity of antigen-specific CD8+ T cell response.

키워드

과제정보

This work was supported by a grant from the National Research Foundation (NRF) funded by the Korean Ministry of Science and ICT (2020R1A5A2031185, 2020M3A9G3080281 and 2022R1A2C2009385) and a grant (HCRI 19001-1*HCRI20012) of Chonnam National University Hwasun Hospital and a new faculty research grant (2020-2029) of Chonnam National University. Figures were drawn using Biorender.com.

참고문헌

  1. Kaech SM, Wherry EJ. Heterogeneity and cell-fate decisions in effector and memory CD8+ T cell differentiation during viral infection. Immunity 2007;27:393-405.
  2. Chang JT, Wherry EJ, Goldrath AW. Molecular regulation of effector and memory T cell differentiation. Nat Immunol 2014;15:1104-1115.
  3. Chen Y, Zander R, Khatun A, Schauder DM, Cui W. Transcriptional and epigenetic regulation of effector and memory CD8 T cell differentiation. Front Immunol 2018;9:2826.
  4. Henning AN, Roychoudhuri R, Restifo NP. Epigenetic control of CD8+ T cell differentiation. Nat Rev Immunol 2018;18:340-356.
  5. Choi JO, Ham JH, Hwang SS. RNA metabolism in T lymphocytes. Immune Netw 2022;22:e39.
  6. Seder RA, Darrah PA, Roederer M. T-cell quality in memory and protection: implications for vaccine design. Nat Rev Immunol 2008;8:247-258.
  7. Kaech SM, Tan JT, Wherry EJ, Konieczny BT, Surh CD, Ahmed R. Selective expression of the interleukin 7 receptor identifies effector CD8 T cells that give rise to long-lived memory cells. Nat Immunol 2003;4:1191-1198.
  8. Sallusto F, Lenig D, Forster R, Lipp M, Lanzavecchia A. Two subsets of memory T lymphocytes with distinct homing potentials and effector functions. Nature 1999;401:708-712.
  9. Wherry EJ, Teichgraber V, Becker TC, Masopust D, Kaech SM, Antia R, von Andrian UH, Ahmed R. Lineage relationship and protective immunity of memory CD8 T cell subsets. Nat Immunol 2003;4:225-234.
  10. Joshi NS, Cui W, Chandele A, Lee HK, Urso DR, Hagman J, Gapin L, Kaech SM. Inflammation directs memory precursor and short-lived effector CD8+ T cell fates via the graded expression of T-bet transcription factor. Immunity 2007;27:281-295.
  11. Olson JA, McDonald-Hyman C, Jameson SC, Hamilton SE. Effector-like CD8+ T cells in the memory population mediate potent protective immunity. Immunity 2013;38:1250-1260.
  12. Masopust D, Vezys V, Marzo AL, Lefrancois L. Preferential localization of effector memory cells in nonlymphoid tissue. Science 2001;291:2413-2417.
  13. Gattinoni L, Zhong XS, Palmer DC, Ji Y, Hinrichs CS, Yu Z, Wrzesinski C, Boni A, Cassard L, Garvin LM, et al. Wnt signaling arrests effector T cell differentiation and generates CD8+ memory stem cells. Nat Med 2009;15:808-813.
  14. Jameson SC, Masopust D. Diversity in T cell memory: an embarrassment of riches. Immunity 2009;31:859-871.
  15. Kaech SM, Cui W. Transcriptional control of effector and memory CD8+ T cell differentiation. Nat Rev Immunol 2012;12:749-761.
  16. Jameson SC, Masopust D. Understanding subset diversity in T cell memory. Immunity 2018;48:214-226.
  17. Omilusik KD, Goldrath AW. Remembering to remember: T cell memory maintenance and plasticity. Curr Opin Immunol 2019;58:89-97.
  18. Arsenio J. Single-cell analysis of CD8 T lymphocyte diversity during adaptive immunity. Wiley Interdiscip Rev Syst Biol Med 2020;12:e1475.
  19. Richard AC. Divide and conquer: phenotypic and temporal heterogeneity within CD8+ T cell responses. Front Immunol 2022;13:949423.
  20. Jameson SC. Maintaining the norm: T-cell homeostasis. Nat Rev Immunol 2002;2:547-556.
  21. Takada K, Jameson SC. Naive T cell homeostasis: from awareness of space to a sense of place. Nat Rev Immunol 2009;9:823-832.
  22. Surh CD, Sprent J. Homeostasis of naive and memory T cells. Immunity 2008;29:848-862.
  23. Sprent J, Surh CD. Normal T cell homeostasis: the conversion of naive cells into memory-phenotype cells. Nat Immunol 2011;12:478-484.
  24. Weninger W, Crowley MA, Manjunath N, von Andrian UH. Migratory properties of naive, effector, and memory CD8+ T cells. J Exp Med 2001;194:953-966.
  25. Sallusto F, Geginat J, Lanzavecchia A. Central memory and effector memory T cell subsets: function, generation, and maintenance. Annu Rev Immunol 2004;22:745-763.
  26. Cho JH, Kim HO, Surh CD, Sprent J. T cell receptor-dependent regulation of lipid rafts controls naive CD8+ T cell homeostasis. Immunity 2010;32:214-226.
  27. Mandl JN, Monteiro JP, Vrisekoop N, Germain RN. T cell-positive selection uses self-ligand binding strength to optimize repertoire recognition of foreign antigens. Immunity 2013;38:263-274.
  28. Persaud SP, Parker CR, Lo WL, Weber KS, Allen PM. Intrinsic CD4+ T cell sensitivity and response to a pathogen are set and sustained by avidity for thymic and peripheral complexes of self peptide and MHC. Nat Immunol 2014;15:266-274.
  29. Fulton RB, Hamilton SE, Xing Y, Best JA, Goldrath AW, Hogquist KA, Jameson SC. The TCR's sensitivity to self peptide-MHC dictates the ability of naive CD8+ T cells to respond to foreign antigens. Nat Immunol 2015;16:107-117.
  30. White JT, Cross EW, Burchill MA, Danhorn T, McCarter MD, Rosen HR, O'Connor B, Kedl RM. Virtual memory T cells develop and mediate bystander protective immunity in an IL-15-dependent manner. Nat Commun 2016;7:11291.
  31. Cho JH, Kim HO, Ju YJ, Kye YC, Lee GW, Lee SW, Yun CH, Bottini N, Webster K, Goodnow CC, et al. CD45-mediated control of TCR tuning in naive and memory CD8+ T cells. Nat Commun 2016;7:13373.
  32. Balyan R, Gund R, Chawla AS, Khare SP, Pradhan SJ, Rane S, Galande S, Durdik JM, George A, Bal V, et al. Correlation of cell-surface CD8 levels with function, phenotype and transcriptome of naive CD8 T cells. Immunology 2019;156:384-401.
  33. De Simone G, Mazza EMC, Cassotta A, Davydov AN, Kuka M, Zanon V, De Paoli F, Scamardella E, Metsger M, Roberto A, et al. CXCR3 identifies human naive CD8+ T cells with enhanced effector differentiation potential. J Immunol 2019;203:3179-3189.
  34. Ju YJ, Lee SW, Kye YC, Lee GW, Kim HO, Yun CH, Cho JH. Self-reactivity controls functional diversity of naive CD8+ T cells by co-opting tonic type I interferon. Nat Commun 2021;12:6059.
  35. Jergovic M, Coplen CP, Uhrlaub JL, Besselsen DG, Cheng S, Smithey MJ, Nikolich-Zugich J. Infectioninduced type I interferons critically modulate the homeostasis and function of CD8+ naive T cells. Nat Commun 2021;12:5303.
  36. Kawabe T, Yi J, Sprent J. Homeostasis of naive and memory T lymphocytes. Cold Spring Harb Perspect Biol 2021;13:a037879.
  37. Tarakhovsky A, Kanner SB, Hombach J, Ledbetter JA, Muller W, Killeen N, Rajewsky K. A role for CD5 in TCR-mediated signal transduction and thymocyte selection. Science 1995;269:535-537.
  38. Azzam HS, Grinberg A, Lui K, Shen H, Shores EW, Love PE. CD5 expression is developmentally regulated by T cell receptor (TCR) signals and TCR avidity. J Exp Med 1998;188:2301-2311.
  39. Azzam HS, DeJarnette JB, Huang K, Emmons R, Park CS, Sommers CL, El-Khoury D, Shores EW, Love PE. Fine tuning of TCR signaling by CD5. J Immunol 2001;166:5464-5472.
  40. Klein L, Kyewski B, Allen PM, Hogquist KA. Positive and negative selection of the T cell repertoire: what thymocytes see (and don't see). Nat Rev Immunol 2014;14:377-391.
  41. Palmer MJ, Mahajan VS, Chen J, Irvine DJ, Lauffenburger DA. Signaling thresholds govern heterogeneity in IL-7-receptor-mediated responses of naive CD8+ T cells. Immunol Cell Biol 2011;89:581-594.
  42. McNeill L, Salmond RJ, Cooper JC, Carret CK, Cassady-Cain RL, Roche-Molina M, Tandon P, Holmes N, Alexander DR. The differential regulation of Lck kinase phosphorylation sites by CD45 is critical for T cell receptor signaling responses. Immunity 2007;27:425-437.
  43. Hermiston ML, Xu Z, Weiss A. CD45: a critical regulator of signaling thresholds in immune cells. Annu Rev Immunol 2003;21:107-137.
  44. Majeti R, Xu Z, Parslow TG, Olson JL, Daikh DI, Killeen N, Weiss A. An inactivating point mutation in the inhibitory wedge of CD45 causes lymphoproliferation and autoimmunity. Cell 2000;103:1059-1070.
  45. Pena-Rossi C, Zuckerman LA, Strong J, Kwan J, Ferris W, Chan S, Tarakhovsky A, Beyers AD, Killeen N. Negative regulation of CD4 lineage development and responses by CD5. J Immunol 1999;163:6494-6501.
  46. Voisinne G, Gonzalez de Peredo A, Roncagalli R. CD5, an Undercover Regulator of TCR Signaling. Front Immunol 2018;9:2900.
  47. Stefanova I, Dorfman JR, Germain RN. Self-recognition promotes the foreign antigen sensitivity of naive T lymphocytes. Nature 2002;420:429-434.
  48. Fischer UB, Jacovetty EL, Medeiros RB, Goudy BD, Zell T, Swanson JB, Lorenz E, Shimizu Y, Miller MJ, Khoruts A, et al. MHC class II deprivation impairs CD4 T cell motility and responsiveness to antigenbearing dendritic cells in vivo. Proc Natl Acad Sci U S A 2007;104:7181-7186.
  49. Hochweller K, Wabnitz GH, Samstag Y, Suffner J, Hammerling GJ, Garbi N. Dendritic cells control T cell tonic signaling required for responsiveness to foreign antigen. Proc Natl Acad Sci U S A 2010;107:5931-5936.
  50. Kim HO, Cho JH. T cell's sense of self: a role of self-recognition in shaping functional competence of naive T cells. Immune Netw 2017;17:201-213.
  51. Surh CD, Sprent J. Homeostatic T cell proliferation: how far can T cells be activated to self-ligands? J Exp Med 2000;192:F9-F14.
  52. Eggert J, Au-Yeung BB. Functional heterogeneity and adaptation of naive T cells in response to tonic TCR signals. Curr Opin Immunol 2021;73:43-49.
  53. Zinzow-Kramer WM, Weiss A, Au-Yeung BB. Adaptation by naive CD4+ T cells to self-antigen-dependent TCR signaling induces functional heterogeneity and tolerance. Proc Natl Acad Sci U S A 2019;116:15160-15169.
  54. Bartleson JM, Viehmann Milam AA, Donermeyer DL, Horvath S, Xia Y, Egawa T, Allen PM. Strength of tonic T cell receptor signaling instructs T follicular helper cell-fate decisions. Nat Immunol 2020;21:1384-1396.
  55. Rogers D, Sood A, Wang H, van Beek JJ, Rademaker TJ, Artusa P, Schneider C, Shen C, Wong DC, Bhagrath A, et al. Pre-existing chromatin accessibility and gene expression differences among naive CD4+ T cells influence effector potential. Cell Reports 2021;37:110064.
  56. Sood A, Lebel ME, Dong M, Fournier M, Vobecky SJ, Haddad E, Delisle JS, Mandl JN, Vrisekoop N, Melichar HJ. CD5 levels define functionally heterogeneous populations of naive human CD4+ T cells. Eur J Immunol 2021;51:1365-1376.
  57. Lee JY, Hamilton SE, Akue AD, Hogquist KA, Jameson SC. Virtual memory CD8 T cells display unique functional properties. Proc Natl Acad Sci U S A 2013;110:13498-13503.
  58. Truckenbrod EN, Jameson SC. The virtuous self-tolerance of virtual memory T cells. EMBO J 2018;37:e99883.
  59. Kieper WC, Burghardt JT, Surh CD. A role for TCR affinity in regulating naive T cell homeostasis. J Immunol 2004;172:40-44.
  60. Tan JT, Dudl E, LeRoy E, Murray R, Sprent J, Weinberg KI, Surh CD. IL-7 is critical for homeostatic proliferation and survival of naive T cells. Proc Natl Acad Sci U S A 2001;98:8732-8737.
  61. Min B, McHugh R, Sempowski GD, Mackall C, Foucras G, Paul WE. Neonates support lymphopeniainduced proliferation. Immunity 2003;18:131-140.
  62. Wojciechowski S, Tripathi P, Bourdeau T, Acero L, Grimes HL, Katz JD, Finkelman FD, Hildeman DA. Bim/Bcl-2 balance is critical for maintaining naive and memory T cell homeostasis. J Exp Med 2007;204:1665-1675.
  63. Li WQ, Guszczynski T, Hixon JA, Durum SK. Interleukin-7 regulates Bim proapoptotic activity in peripheral T-cell survival. Mol Cell Biol 2010;30:590-600.
  64. Pearson C, Silva A, Saini M, Seddon B. IL-7 determines the homeostatic fitness of T cells by distinct mechanisms at different signalling thresholds in vivo. Eur J Immunol 2011;41:3656-3666.
  65. Renkema KR, Lee JY, Lee YJ, Hamilton SE, Hogquist KA, Jameson SC. IL-4 sensitivity shapes the peripheral CD8+ T cell pool and response to infection. J Exp Med 2016;213:1319-1329.
  66. Akue AD, Lee JY, Jameson SC. Derivation and maintenance of virtual memory CD8 T cells. J Immunol 2012;188:2516-2523.
  67. Lee YJ, Holzapfel KL, Zhu J, Jameson SC, Hogquist KA. Steady-state production of IL-4 modulates immunity in mouse strains and is determined by lineage diversity of iNKT cells. Nat Immunol 2013;14:1146-1154.
  68. Kurzweil V, LaRoche A, Oliver PM. Increased peripheral IL-4 leads to an expanded virtual memory CD8+ population. J Immunol 2014;192:5643-5651.
  69. Gough DJ, Messina NL, Clarke CJ, Johnstone RW, Levy DE. Constitutive type I interferon modulates homeostatic balance through tonic signaling. Immunity 2012;36:166-174.
  70. Uccellini MB, Garcia-Sastre A. ISRE-reporter mouse reveals high basal and induced type I IFN responses in inflammatory monocytes. Cell Reports 2018;25:2784-2796.e3.
  71. Yu Q, Katlinskaya YV, Carbone CJ, Zhao B, Katlinski KV, Zheng H, Guha M, Li N, Chen Q, Yang T, et al. DNA-damage-induced type I interferon promotes senescence and inhibits stem cell function. Cell Reports 2015;11:785-797.
  72. Hartlova A, Erttmann SF, Raffi FA, Schmalz AM, Resch U, Anugula S, Lienenklaus S, Nilsson LM, Kroger A, Nilsson JA, et al. DNA damage primes the type I interferon system via the cytosolic DNA sensor STING to promote anti-microbial innate immunity. Immunity 2015;42:332-343.
  73. Lienenklaus S, Cornitescu M, Zietara N, Lyszkiewicz M, Gekara N, Jablonska J, Edenhofer F, Rajewsky K, Bruder D, Hafner M, et al. Novel reporter mouse reveals constitutive and inflammatory expression of IFN-β in vivo. J Immunol 2009;183:3229-3236.
  74. Xing Y, Wang X, Jameson SC, Hogquist KA. Late stages of T cell maturation in the thymus involve NF-κB and tonic type I interferon signaling. Nat Immunol 2016;17:565-573.
  75. Martinet V, Tonon S, Torres D, Azouz A, Nguyen M, Kohler A, Flamand V, Mao CA, Klein WH, Leo O, et al. Type I interferons regulate eomesodermin expression and the development of unconventional memory CD8+ T cells. Nat Commun 2015;6:7089.
  76. Rubtsov YP, Rudensky AY. TGFβ signalling in control of T-cell-mediated self-reactivity. Nat Rev Immunol 2007;7:443-453.
  77. Johnson LD, Jameson SC. TGF-β sensitivity restrains CD8+ T cell homeostatic proliferation by enforcing sensitivity to IL-7 and IL-15. PLoS One 2012;7:e42268.
  78. Gorelik L, Flavell RA. Abrogation of TGFβ signaling in T cells leads to spontaneous T cell differentiation and autoimmune disease. Immunity 2000;12:171-181.
  79. Lucas PJ, Kim SJ, Melby SJ, Gress RE. Disruption of T cell homeostasis in mice expressing a T cell-specific dominant negative transforming growth factor β II receptor. J Exp Med 2000;191:1187-1196.
  80. Li MO, Sanjabi S, Flavell RA. Transforming growth factor-beta controls development, homeostasis, and tolerance of T cells by regulatory T cell-dependent and -independent mechanisms. Immunity 2006;25:455-471.
  81. Mani V, Bromley SK, Aijo T, Mora-Buch R, Carrizosa E, Warner RD, Hamze M, Sen DR, Chasse AY, Lorant A, et al. Migratory DCs activate TGF-β to precondition naive CD8+ T cells for tissue-resident memory fate. Science 2019;366:eaav5728.
  82. Smith NL, Patel RK, Reynaldi A, Grenier JK, Wang J, Watson NB, Nzingha K, Yee Mon KJ, Peng SA, Grimson A, et al. Developmental Origin Governs CD8+ T Cell Fate Decisions during Infection. Cell 2018;174:117-130.e14.
  83. Nikolich-Zugich J, Li G, Uhrlaub JL, Renkema KR, Smithey MJ. Age-related changes in CD8 T cell homeostasis and immunity to infection. Semin Immunol 2012;24:356-364.
  84. Qi Q, Zhang DW, Weyand CM, Goronzy JJ. Mechanisms shaping the naive T cell repertoire in the elderly-thymic involution or peripheral homeostatic proliferation? Exp Gerontol 2014;54:71-74.
  85. den Braber I, Mugwagwa T, Vrisekoop N, Westera L, Mogling R, de Boer AB, Willems N, Schrijver EH, Spierenburg G, Gaiser K, et al. Maintenance of peripheral naive T cells is sustained by thymus output in mice but not humans. Immunity 2012;36:288-297.
  86. Linton PJ, Dorshkind K. Age-related changes in lymphocyte development and function. Nat Immunol 2004;5:133-139.
  87. Goronzy JJ, Weyand CM. Mechanisms underlying T cell ageing. Nat Rev Immunol 2019;19:573-583.
  88. Das A, Rouault-Pierre K, Kamdar S, Gomez-Tourino I, Wood K, Donaldson I, Mein CA, Bonnet D, Hayday AC, Gibbons DL. Adaptive from innate: human IFN-γ+CD4+ T cells can arise directly from CXCL8- producing recent thymic emigrants in babies and adults. J Immunol 2017;199:1696-1705.
  89. Galindo-Albarran AO, Lopez-Portales OH, Gutierrez-Reyna DY, Rodriguez-Jorge O, Sanchez-Villanueva JA, Ramirez-Pliego O, Bergon A, Loriod B, Holota H, Imbert J, et al. CD8+ T Cells from human neonates are biased toward an innate immune response. Cell Reports 2016;17:2151-2160.
  90. Hamilton SE, Jameson SC. CD8 T cell quiescence revisited. Trends Immunol 2012;33:224-230.
  91. Neama AF, Looi CY, Wong WF. 5. Multiple players in the mechanical control of T cell quiescence. In: Isvoranu G, ed. Lymphocyte Updates. London: IntechOpen; 2017.
  92. ElTanbouly MA, Noelle RJ. Rethinking peripheral T cell tolerance: checkpoints across a T cell's journey. Nat Rev Immunol 2021;21:257-267.
  93. Yusuf I, Fruman DA. Regulation of quiescence in lymphocytes. Trends Immunol 2003;24:380-386.
  94. Feng X, Wang H, Takata H, Day TJ, Willen J, Hu H. Transcription factor Foxp1 exerts essential cellintrinsic regulation of the quiescence of naive T cells. Nat Immunol 2011;12:544-550.
  95. Kye YC, Lee GW, Lee SW, Ju YJ, Kim HO, Yun CH, Cho JH. STAT1 maintains naive CD8+ T cell quiescence by suppressing the type I IFN-STAT4-mTORC1 signaling axis. Sci Adv 2021;7:eabg8764.
  96. ElTanbouly MA, Zhao Y, Nowak E, Li J, Schaafsma E, Le Mercier I, Ceeraz S, Lines JL, Peng C, Carriere C, et al. VISTA is a checkpoint regulator for naive T cell quiescence and peripheral tolerance. Science 2020;367:eaay0524.
  97. Buang N, Tapeng L, Gray V, Sardini A, Whilding C, Lightstone L, Cairns TD, Pickering MC, Behmoaras J, Ling GS, et al. Type I interferons affect the metabolic fitness of CD8+ T cells from patients with systemic lupus erythematosus. Nat Commun 2021;12:1980.
  98. Altorok N, Coit P, Hughes T, Koelsch KA, Stone DU, Rasmussen A, Radfar L, Scofield RH, Sivils KL, Farris AD, et al. Genome-wide DNA methylation patterns in naive CD4+ T cells from patients with primary Sjogren's syndrome. Arthritis Rheumatol 2014;66:731-739.
  99. Coit P, Dozmorov MG, Merrill JT, McCune WJ, Maksimowicz-McKinnon K, Wren JD, Sawalha AH. Epigenetic reprogramming in naive CD4+ T cells favoring T cell activation and non-Th1 effector T cell immune response as an early event in lupus flares. Arthritis Rheumatol 2016;68:2200-2209.
  100. Heninger AK, Eugster A, Kuehn D, Buettner F, Kuhn M, Lindner A, Dietz S, Jergens S, Wilhelm C, Beyerlein A, et al. A divergent population of autoantigen-responsive CD4+ T cells in infants prior to β cell autoimmunity. Sci Transl Med 2017;9:eaaf8848.