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T Cell Subsets and Immune Homeostasis

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Immune Homeostasis

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2782))

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Abstract

T cells are a heterogeneous group of cells that can be classified into different subtypes according to different classification methods. The body’s immune system has a highly complex and effective regulatory network that allows for the relative stability of immune system function. Maintaining proper T cell homeostasis is essential for promoting protective immunity and limiting autoimmunity and tumor formation. Among the T cell family members, more and more T cell subsets have gradually been characterized. In this chapter, we summarize the functions of some key T cell subsets and their impact on immune homeostasis.

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References

  1. Kumar BV, Connors TJ, Farber DL (2018) Human T cell development, localization, and function throughout life. Immunity 48:202–213

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Guerder S, Flavell RA (1995) T-cell activation. Two for T. Curr Biol 5:866–868

    Article  CAS  PubMed  Google Scholar 

  3. Hedrick SM, Sharp LL (1998) T-cell fate. Immunol Rev 165:95–110

    Google Scholar 

  4. Santamaria J, Darrigues J, van Meerwijk JPM, Romagnoli P (2018) Antigen-presenting cells and T-lymphocytes homing to the thymus shape T cell development. Immunol Lett 204:9–15

    Article  CAS  PubMed  Google Scholar 

  5. Koch U, Radtke F (2011) Mechanisms of T cell development and transformation. Annu Rev Cell Dev Biol 27:539–562

    Article  CAS  PubMed  Google Scholar 

  6. Altin JG, Sloan EK (1997) The role of CD45 and CD45-associated molecules in T cell activation. Immunol Cell Biol 75:430–445

    Article  CAS  PubMed  Google Scholar 

  7. Jung Y, Wen L, Altman A, Ley K (2021) CD45 pre-exclusion from the tips of T cell microvilli prior to antigen recognition. Nat Commun 12:3872

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Malissen B, Ardouin L, Lin SY, Gillet A, Malissen M (1999) Function of the CD3 subunits of the pre-TCR and TCR complexes during T cell development. Adv Immunol 72:103–148

    CAS  PubMed  Google Scholar 

  9. Crimeen-Irwin B, Scalzo K, Gloster S, Mottram PL, Plebanski M (2005) Failure of immune homeostasis – the consequences of under and over reactivity. Curr Drug Targets Immune Endocr Metabol Disord 5:413–422

    Article  CAS  PubMed  Google Scholar 

  10. Morath A, Schamel WW (2020) αβ and γδ T cell receptors: similar but different. J Leukoc Biol 107:1045–1055

    Article  CAS  PubMed  Google Scholar 

  11. Nielsen MM, Witherden DA, Havran WL (2017) γδ T cells in homeostasis and host defence of epithelial barrier tissues. Nat Rev Immunol 17:733–745

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Rigau M, Ostrouska S, Fulford TS, Johnson DN, Woods K, Ruan Z, McWilliam HEG, Hudson C, Tutuka C, Wheatley AK, Kent SJ, Villadangos JA, Pal B, Kurts C, Simmonds J, Pelzing M, Nash AD, Hammet A, Verhagen AM, Vairo G, Maraskovsky E, Panousis C, Gherardin NA, Cebon J, Godfrey DI, Behren A, Uldrich AP (2020) Butyrophilin 2A1 is essential for phosphoantigen reactivity by γδ T cells. Science 367:eaay5516

    Article  CAS  PubMed  Google Scholar 

  13. Dimova T, Brouwer M, Gosselin F, Tassignon J, Leo O, Donner C, Marchant A, Vermijlen D (2015) Effector Vγ9Vδ2 T cells dominate the human fetal γδ T-cell repertoire. Proc Natl Acad Sci U S A 112:E556–E565

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. McVay LD, Carding SR, Bottomly K, Hayday AC (1991) Regulated expression and structure of T cell receptor gamma/delta transcripts in human thymic ontogeny. EMBO J 10:83–91

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Tan L, Sandrock I, Odak I, Aizenbud Y, Wilharm A, Barros-Martins J, Tabib Y, Borchers A, Amado T, Gangoda L, Herold MJ, Schmidt-Supprian M, Kisielow J, Silva-Santos B, Koenecke C, Hovav A-H, Krebs C, Prinz I, Ravens S (2019) Single-cell transcriptomics identifies the adaptation of Scart1+ Vγ6+ T cells to skin residency as activated effector cells. Cell Rep 27:3657–3671.e4

    Article  CAS  PubMed  Google Scholar 

  16. Marchitto MC, Dillen CA, Liu H, Miller RJ, Archer NK, Ortines RV, Alphonse MP, Marusina AI, Merleev AA, Wang Y, Pinsker BL, Byrd AS, Brown ID, Ravipati A, Zhang E, Cai SS, Limjunyawong N, Dong X, Yeaman MR, Simon SI, Shen W, Durum SK, O’Brien RL, Maverakis E, Miller LS (2019) Clonal Vγ6+Vδ4+ T cells promote IL-17-mediated immunity against Staphylococcus aureus skin infection. Proc Natl Acad Sci U S A 116:10917–10926

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Muñoz-Ruiz M, Sumaria N, Pennington DJ, Silva-Santos B (2017) Thymic determinants of γδ T cell differentiation. Trends Immunol 38:336–344

    Article  PubMed  Google Scholar 

  18. Isailovic N, Daigo K, Mantovani A, Selmi C (2015) Interleukin-17 and innate immunity in infections and chronic inflammation. J Autoimmun 60:1–11

    Article  CAS  PubMed  Google Scholar 

  19. Hirota K, Turner J-E, Villa M, Duarte JH, Demengeot J, Steinmetz OM, Stockinger B (2013) Plasticity of Th17 cells in Peyer’s patches is responsible for the induction of T cell-dependent IgA responses. Nat Immunol 14:372–379

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Papotto PH, Reinhardt A, Prinz I, Silva-Santos B (2018) Innately versatile: γδ17 T cells in inflammatory and autoimmune diseases. J Autoimmun 87:26–37

    Article  CAS  PubMed  Google Scholar 

  21. Schirmer L, Rothhammer V, Hemmer B, Korn T (2013) Enriched CD161high CCR6+ γδ T cells in the cerebrospinal fluid of patients with multiple sclerosis. JAMA Neurol 70:345–351

    Article  PubMed  Google Scholar 

  22. Kurasawa K, Hirose K, Sano H, Endo H, Shinkai H, Nawata Y, Takabayashi K, Iwamoto I (2000) Increased interleukin-17 production in patients with systemic sclerosis. Arthritis Rheum 43:2455–2463

    Article  CAS  PubMed  Google Scholar 

  23. Prager I, Liesche C, van Ooijen H, Urlaub D, Verron Q, Sandström N, Fasbender F, Claus M, Eils R, Beaudouin J, Önfelt B, Watzl C (2019) NK cells switch from granzyme B to death receptor-mediated cytotoxicity during serial killing. J Exp Med 216:2113–2127

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Voskoboinik I, Whisstock JC, Trapani JA (2015) Perforin and granzymes: function, dysfunction and human pathology. Nat Rev Immunol 15:388–400

    Article  CAS  PubMed  Google Scholar 

  25. Etxeberria I, Glez-Vaz J, Teijeira Á, Melero I (2020) New emerging targets in cancer immunotherapy: CD137/4-1BB costimulatory axis. ESMO Open 4:e000733

    Article  PubMed  PubMed Central  Google Scholar 

  26. den Braber I, Mugwagwa T, Vrisekoop N, Westera L, Mögling R, de Boer AB, Willems N, Schrijver EHR, Spierenburg G, Gaiser K, Mul E, Otto SA, Ruiter AFC, Ackermans MT, Miedema F, Borghans JAM, de Boer RJ, Tesselaar K (2012) Maintenance of peripheral naive T cells is sustained by thymus output in mice but not humans. Immunity 36:288–297

    Article  Google Scholar 

  27. Cieri N, Camisa B, Cocchiarella F, Forcato M, Oliveira G, Provasi E, Bondanza A, Bordignon C, Peccatori J, Ciceri F, Lupo-Stanghellini MT, Mavilio F, Mondino A, Bicciato S, Recchia A, Bonini C (2013) IL-7 and IL-15 instruct the generation of human memory stem T cells from naive precursors. Blood 121:573–584

    Article  CAS  PubMed  Google Scholar 

  28. Cimbro R, Vassena L, Arthos J, Cicala C, Kehrl JH, Park C, Sereti I, Lederman MM, Fauci AS, Lusso P (2012) IL-7 induces expression and activation of integrin α4β7 promoting naive T-cell homing to the intestinal mucosa. Blood 120:2610–2619

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Surh CD, Sprent J (2008) Homeostasis of naive and memory T cells. Immunity 29:848–862

    Article  CAS  PubMed  Google Scholar 

  30. Vivien L, Benoist C, Mathis D (2001) T lymphocytes need IL-7 but not IL-4 or IL-6 to survive in vivo. Int Immunol 13:763–768

    Article  CAS  PubMed  Google Scholar 

  31. Tan JT, Dudl E, LeRoy E, Murray R, Sprent J, Weinberg KI, Surh CD (2001) IL-7 is critical for homeostatic proliferation and survival of naive T cells. Proc Natl Acad Sci U S A 98:8732–8737

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Raeber ME, Zurbuchen Y, Impellizzieri D, Boyman O (2018) The role of cytokines in T-cell memory in health and disease. Immunol Rev 283:176–193

    Article  CAS  PubMed  Google Scholar 

  33. Takamura S (2020) Divergence of tissue-memory T cells: distribution and function-based classification. Cold Spring Harb Perspect Biol 12:a037762

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Mueller SN, Gebhardt T, Carbone FR, Heath WR (2013) Memory T cell subsets, migration patterns, and tissue residence. Annu Rev Immunol 31:137–161

    Article  CAS  PubMed  Google Scholar 

  35. Turner DL, Bickham KL, Thome JJ, Kim CY, D’Ovidio F, Wherry EJ, Farber DL (2014) Lung niches for the generation and maintenance of tissue-resident memory T cells. Mucosal Immunol 7:501–510

    Article  CAS  PubMed  Google Scholar 

  36. Teijaro JR, Turner D, Pham Q, Wherry EJ, Lefrançois L, Farber DL (2011) Cutting edge: tissue-retentive lung memory CD4 T cells mediate optimal protection to respiratory virus infection. J Immunol 187:5510–5514

    Article  CAS  PubMed  Google Scholar 

  37. Herndler-Brandstetter D, Landgraf K, Jenewein B, Tzankov A, Brunauer R, Brunner S, Parson W, Kloss F, Gassner R, Lepperdinger G, Grubeck-Loebenstein B (2011) Human bone marrow hosts polyfunctional memory CD4+ and CD8+ T cells with close contact to IL-15-producing cells. J Immunol 186:6965–6971

    Article  CAS  PubMed  Google Scholar 

  38. Radbruch A, McGrath MA, Siracusa F, Hoffmann U, Sercan-Alp Ö, Hutloff A, Tokoyoda K, Chang H-D, Dong J (2021) Homeostasis and durability of T-cell memory-the resting and the restless T-cell memory. Cold Spring Harb Perspect Biol 13:a038083

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Becker TC, Coley SM, Wherry EJ, Ahmed R (2005) Bone marrow is a preferred site for homeostatic proliferation of memory CD8 T cells. J Immunol 174:1269–1273

    Article  CAS  PubMed  Google Scholar 

  40. Kondrack RM, Harbertson J, Tan JT, McBreen ME, Surh CD, Bradley LM (2003) Interleukin 7 regulates the survival and generation of memory CD4 cells. J Exp Med 198:1797–1806

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Li J, Huston G, Swain SL (2003) IL-7 promotes the transition of CD4 effectors to persistent memory cells. J Exp Med 198:1807–1815

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Becker TC, Wherry EJ, Boone D, Murali-Krishna K, Antia R, Ma A, Ahmed R (2002) Interleukin 15 is required for proliferative renewal of virus-specific memory CD8 T cells. J Exp Med 195:1541–1548

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Goldrath AW, Sivakumar PV, Glaccum M, Kennedy MK, Bevan MJ, Benoist C, Mathis D, Butz EA (2002) Cytokine requirements for acute and Basal homeostatic proliferation of naive and memory CD8+ T cells. J Exp Med 195:1515–1522

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Kolan SS, Li G, Wik JA, Malachin G, Guo S, Kolan P, Skålhegg BS (2020) Cellular metabolism dictates T cell effector function in health and disease. Scand J Immunol 92:e12956

    Article  CAS  PubMed  Google Scholar 

  45. Weigelin B, Krause M, Friedl P (2011) Cytotoxic T lymphocyte migration and effector function in the tumor microenvironment. Immunol Lett 138:19–21

    Article  CAS  PubMed  Google Scholar 

  46. Mosmann TR, Li L, Sad S (1997) Functions of CD8 T-cell subsets secreting different cytokine patterns. Semin Immunol 9:87–92

    Article  CAS  PubMed  Google Scholar 

  47. Cao X, Cai SF, Fehniger TA, Song J, Collins LI, Piwnica-Worms DR, Ley TJ (2007) Granzyme B and perforin are important for regulatory T cell-mediated suppression of tumor clearance. Immunity 27:635–646

    Article  CAS  PubMed  Google Scholar 

  48. Jonsson AH, Zhang F, Dunlap G, Gomez-Rivas E, Watts GFM, Faust HJ, Rupani KV, Mears JR, Meednu N, Wang R, Keras G, Coblyn JS, Massarotti EM, Todd DJ, Anolik JH, McDavid A, Wei K, Rao DA, Raychaudhuri S, Brenner MB (2022) Granzyme K+ CD8 T cells form a core population in inflamed human tissue. Sci Transl Med 14:eabo0686

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Flores-Mendoza G, Rodríguez-Rodríguez N, Rubio RM, Madera-Salcedo IK, Rosetti F, Crispín JC (2021) Fas/FasL signaling regulates CD8 expression during exposure to self-antigens. Front Immunol 12:635862

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Yajima T, Hoshino K, Muranushi R, Mogi A, Onozato R, Yamaki E, Kosaka T, Tanaka S, Shirabe K, Yoshikai Y, Kuwano H (2019) Fas/FasL signaling is critical for the survival of exhausted antigen-specific CD8+ T cells during tumor immune response. Mol Immunol 107:97–105

    Article  CAS  PubMed  Google Scholar 

  51. Saravia J, Chapman NM, Chi H (2019) Helper T cell differentiation. Cell Mol Immunol 16:634–643

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Zhu J, Paul WE (2008) CD4 T cells: fates, functions, and faults. Blood 112:1557–1569

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Romagnani S (1999) Th1/Th2 cells. Inflamm Bowel Dis 5:285–294

    Article  CAS  PubMed  Google Scholar 

  54. Krueger PD, Goldberg MF, Hong S-W, Osum KC, Langlois RA, Kotov DI, Dileepan T, Jenkins MK (2021) Two sequential activation modules control the differentiation of protective T helper-1 (Th1) cells. Immunity 54:687–701.e4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Bagheri N, Salimzadeh L, Shirzad H (2018) The role of T helper 1-cell response in Helicobacter pylori-infection. Microb Pathog 123:1–8

    Article  CAS  PubMed  Google Scholar 

  56. Ma J, Chen T, Mandelin J, Ceponis A, Miller NE, Hukkanen M, Ma GF, Konttinen YT (2003) Regulation of macrophage activation. Cell Mol Life Sci 60:2334–2346

    Article  CAS  PubMed  Google Scholar 

  57. Ogawa A, Yoshizaki A, Yanaba K, Ogawa F, Hara T, Muroi E, Takenaka M, Shimizu K, Hasegawa M, Fujimoto M, Tedder TF, Sato S (2010) The differential role of L-selectin and ICAM-1 in Th1-type and Th2-type contact hypersensitivity. J Invest Dermatol 130:1558–1570

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Snell LM, Osokine I, Yamada DH, De la Fuente JR, Elsaesser HJ, Brooks DG (2016) Overcoming CD4 Th1 cell fate restrictions to sustain antiviral CD8 T cells and control persistent virus infection. Cell Rep 16:3286–3296

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Zoldan K, Ehrlich S, Killmer S, Wild K, Smits M, Russ M, Globig A-M, Hofmann M, Thimme R, Boettler T (2021) Th1-biased hepatitis C virus-specific follicular T helper-like cells effectively support B cells after antiviral therapy. Front Immunol 12:742061

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Smith KM, Brewer JM, Rush CM, Riley J, Garside P (2004) In vivo generated Th1 cells can migrate to B cell follicles to support B cell responses. J Immunol 173:1640–1646

    Article  CAS  PubMed  Google Scholar 

  61. Ruterbusch M, Pruner KB, Shehata L, Pepper M (2020) In vivo CD4+ T cell differentiation and function: revisiting the Th1/Th2 paradigm. Annu Rev Immunol 38:705–725

    Article  CAS  PubMed  Google Scholar 

  62. Aalberse RC, Platts-Mills TAE (2004) How do we avoid developing allergy: modifications of the TH2 response from a B-cell perspective. J Allergy Clin Immunol 113:983–986

    Article  CAS  PubMed  Google Scholar 

  63. Ogulur I, Pat Y, Ardicli O, Barletta E, Cevhertas L, Fernandez-Santamaria R, Huang M, Bel Imam M, Koch J, Ma S, Maurer DJ, Mitamura Y, Peng Y, Radzikowska U, Rinaldi AO, Rodriguez-Coira J, Satitsuksanoa P, Schneider SR, Wallimann A, Zhakparov D, Ziadlou R, Brüggen M-C, van de Veen W, Sokolowska M, Baerenfaller K, Zhang L, Akdis M, Akdis CA (2021) Advances and highlights in biomarkers of allergic diseases. Allergy 76:3659–3686

    Article  PubMed  Google Scholar 

  64. Nakayama T, Hirahara K, Onodera A, Endo Y, Hosokawa H, Shinoda K, Tumes DJ, Okamoto Y (2017) Th2 cells in health and disease. Annu Rev Immunol 35:53–84

    Article  CAS  PubMed  Google Scholar 

  65. Turner H, Kinet JP (1999) Signalling through the high-affinity IgE receptor Fc epsilonRI. Nature 402:B24–B30

    Article  CAS  PubMed  Google Scholar 

  66. Abdelaziz MH, Wang H, Cheng J, Xu H (2020) Th2 cells as an intermediate for the differentiation of naïve T cells into Th9 cells, associated with the Smad3/Smad4 and IRF4 pathway. Exp Ther Med 19:1947–1954

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Olson MR, Kaplan MH (2019) TH9 immunodeficiency in patients with hyper-IgE syndrome. J Allergy Clin Immunol 143:935–936

    Article  PubMed  Google Scholar 

  68. Licona-Limón P, Arias-Rojas A, Olguín-Martínez E (2017) IL-9 and Th9 in parasite immunity. Semin Immunopathol 39:29–38

    Article  PubMed  Google Scholar 

  69. Fu Y, Wang J, Zhou B, Pajulas A, Gao H, Ramdas B, Koh B, Ulrich BJ, Yang S, Kapur R, Renauld J-C, Paczesny S, Liu Y, Tighe RM, Licona-Limón P, Flavell RA, Takatsuka S, Kitamura D, Tepper RS, Sun J, Kaplan MH (2022) An IL-9-pulmonary macrophage axis defines the allergic lung inflammatory environment. Sci Immunol 7:eabi9768

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Lu Y, Wang Q, Xue G, Bi E, Ma X, Wang A, Qian J, Dong C, Yi Q (2018) Th9 cells represent a unique subset of CD4+ T cells endowed with the ability to eradicate advanced tumors. Cancer Cell 33:1048–1060.e7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Sallusto F, Zielinski CE, Lanzavecchia A (2012) Human Th17 subsets. Eur J Immunol 42:2215–2220

    Article  CAS  PubMed  Google Scholar 

  72. Zhang W, Liu X, Zhu Y, Liu X, Gu Y, Dai X, Li B (2021) Transcriptional and posttranslational regulation of Th17/Treg balance in health and disease. Eur J Immunol 51:2137–2150

    Article  CAS  PubMed  Google Scholar 

  73. Kumar R, Theiss AL, Venuprasad K (2021) RORγt protein modifications and IL-17-mediated inflammation. Trends Immunol 42:1037–1050

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Lee GR (2018) The balance of Th17 versus treg cells in autoimmunity. Int J Mol Sci 19:730

    Article  PubMed  PubMed Central  Google Scholar 

  75. Bettelli E, Korn T, Oukka M, Kuchroo VK (2008) Induction and effector functions of T(H)17 cells. Nature 453:1051–1057

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Lock C, Hermans G, Pedotti R, Brendolan A, Schadt E, Garren H, Langer-Gould A, Strober S, Cannella B, Allard J, Klonowski P, Austin A, Lad N, Kaminski N, Galli SJ, Oksenberg JR, Raine CS, Heller R, Steinman L (2002) Gene-microarray analysis of multiple sclerosis lesions yields new targets validated in autoimmune encephalomyelitis. Nat Med 8:500–508

    Article  CAS  PubMed  Google Scholar 

  77. Noack M, Miossec P (2014) Th17 and regulatory T cell balance in autoimmune and inflammatory diseases. Autoimmun Rev 13:668–677

    Article  CAS  PubMed  Google Scholar 

  78. Kikuchi J, Hashizume M, Kaneko Y, Yoshimoto K, Nishina N, Takeuchi T (2015) Peripheral blood CD4(+)CD25(+)CD127(low) regulatory T cells are significantly increased by tocilizumab treatment in patients with rheumatoid arthritis: increase in regulatory T cells correlates with clinical response. Arthritis Res Ther 17:10

    Article  PubMed  PubMed Central  Google Scholar 

  79. Samson M, Audia S, Janikashvili N, Ciudad M, Trad M, Fraszczak J, Ornetti P, Maillefert J-F, Miossec P, Bonnotte B (2012) Brief report: inhibition of interleukin-6 function corrects Th17/Treg cell imbalance in patients with rheumatoid arthritis. Arthritis Rheum 64:2499–2503

    Article  CAS  PubMed  Google Scholar 

  80. Lee J, Baek S, Lee J, Lee J, Lee D-G, Park M-K, Cho M-L, Park S-H, Kwok S-K (2015) Digoxin ameliorates autoimmune arthritis via suppression of Th17 differentiation. Int Immunopharmacol 26:103–111

    Article  CAS  PubMed  Google Scholar 

  81. Doulabi H, Masoumi E, Rastin M, Foolady Azarnaminy A, Esmaeili S-A, Mahmoudi M (2022) The role of Th22 cells, from tissue repair to cancer progression. Cytokine 149:155749

    Article  CAS  PubMed  Google Scholar 

  82. Dudakov JA, Hanash AM, van den Brink MRM (2015) Interleukin-22: immunobiology and pathology. Annu Rev Immunol 33:747–785

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Andoh A, Zhang Z, Inatomi O, Fujino S, Deguchi Y, Araki Y, Tsujikawa T, Kitoh K, Kim-Mitsuyama S, Takayanagi A, Shimizu N, Fujiyama Y (2005) Interleukin-22, a member of the IL-10 subfamily, induces inflammatory responses in colonic subepithelial myofibroblasts. Gastroenterology 129:969–984

    Article  CAS  PubMed  Google Scholar 

  84. Abadi AH, Mahdavi M, Khaledi A, Esmaeili S-A, Esmaeili D, Sahebkar A (2018) Study of serum bactericidal and splenic activity of Total-OMP- CagA combination from Brucella abortus and Helicobacter pylori in BALB/c mouse model. Microb Pathog 121:100–105

    Article  CAS  PubMed  Google Scholar 

  85. Ouyang W, O’Garra A (2019) IL-10 family cytokines IL-10 and IL-22: from basic science to clinical translation. Immunity 50:871–891

    Article  CAS  PubMed  Google Scholar 

  86. Aujla SJ, Chan YR, Zheng M, Fei M, Askew DJ, Pociask DA, Reinhart TA, McAllister F, Edeal J, Gaus K, Husain S, Kreindler JL, Dubin PJ, Pilewski JM, Myerburg MM, Mason CA, Iwakura Y, Kolls JK (2008) IL-22 mediates mucosal host defense against Gram-negative bacterial pneumonia. Nat Med 14:275–281

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Jiang Q, Yang G, Xiao F, Xie J, Wang S, Lu L, Cui D (2021) Role of Th22 cells in the pathogenesis of autoimmune diseases. Front Immunol 12:688066

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Olatunde AC, Hale JS, Lamb TJ (2021) Cytokine-skewed Tfh cells: functional consequences for B cell help. Trends Immunol 42:536–550

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Crotty S (2011) Follicular helper CD4 T cells (TFH). Annu Rev Immunol 29:621–663

    Article  CAS  PubMed  Google Scholar 

  90. Choi J, Crotty S (2021) Bcl6-mediated transcriptional regulation of follicular helper T cells (TFH). Trends Immunol 42:336–349

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Rauschmeier R, Reinhardt A, Gustafsson C, Glaros V, Artemov AV, Dunst J, Taneja R, Adameyko I, Månsson R, Busslinger M, Kreslavsky T (2022) Bhlhe40 function in activated B and TFH cells restrains the GC reaction and prevents lymphomagenesis. J Exp Med 219:e20211406

    Article  CAS  PubMed  Google Scholar 

  92. Ueno H, Banchereau J, Vinuesa CG (2015) Pathophysiology of T follicular helper cells in humans and mice. Nat Immunol 16:142–152

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Nakayamada S, Takahashi H, Kanno Y, O’Shea JJ (2012) Helper T cell diversity and plasticity. Curr Opin Immunol 24:297–302

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Ma X, Nakayamada S (2021) Multi-source pathways of T follicular helper cell differentiation. Front Immunol 12:621105

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Fonseca VR, Ribeiro F, Graca L (2019) T follicular regulatory (Tfr) cells: dissecting the complexity of Tfr-cell compartments. Immunol Rev 288:112–127

    Article  CAS  PubMed  Google Scholar 

  96. Ding T, Su R, Wu R, Xue H, Wang Y, Su R, Gao C, Li X, Wang C (2021) Frontiers of autoantibodies in autoimmune disorders: crosstalk between Tfh/Tfr and regulatory B cells. Front Immunol 12:641013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Wei X, Niu X (2022) T follicular helper cells in autoimmune diseases. J Autoimmun 134:102976

    Article  PubMed  Google Scholar 

  98. Zhang Q, Xiang L, Zaman MH, Dong W, He G, Deng G-M (2019) Predominant role of immunoglobulin G in the pathogenesis of splenomegaly in murine lupus. Front Immunol 10:3020

    Article  CAS  PubMed  Google Scholar 

  99. Wichner K, Stauss D, Kampfrath B, Krüger K, Müller G, Rehm A, Lipp M, Höpken UE (2016) Dysregulated development of IL-17- and IL-21-expressing follicular helper T cells and increased germinal center formation in the absence of RORγt. FASEB J 30:761–774

    Article  CAS  PubMed  Google Scholar 

  100. Lu J, Wu J, Xia X, Peng H, Wang S (2021) Follicular helper T cells: potential therapeutic targets in rheumatoid arthritis. Cell Mol Life Sci 78:5095–5106

    Article  CAS  PubMed  Google Scholar 

  101. Ohkura N, Hamaguchi M, Morikawa H, Sugimura K, Tanaka A, Ito Y, Osaki M, Tanaka Y, Yamashita R, Nakano N, Huehn J, Fehling HJ, Sparwasser T, Nakai K, Sakaguchi S (2012) T cell receptor stimulation-induced epigenetic changes and Foxp3 expression are independent and complementary events required for Treg cell development. Immunity 37:785–799

    Article  CAS  PubMed  Google Scholar 

  102. Shevyrev D, Tereshchenko V (2019) Treg heterogeneity, function, and homeostasis. Front Immunol 10:3100

    Article  CAS  PubMed  Google Scholar 

  103. Benoist C, Mathis D (2012) Treg cells, life history, and diversity. Cold Spring Harb Perspect Biol 4:a007021

    Article  PubMed  PubMed Central  Google Scholar 

  104. Song Y, Wang N, Chen L, Fang L (2021) Tr1 cells as a key regulator for maintaining immune homeostasis in transplantation. Front Immunol 12:671579

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Battaglia M, Gregori S, Bacchetta R, Roncarolo M-G (2006) Tr1 cells: from discovery to their clinical application. Semin Immunol 18:120–127

    Article  CAS  PubMed  Google Scholar 

  106. Carrier Y, Yuan J, Kuchroo VK, Weiner HL (2007) Th3 cells in peripheral tolerance. II. TGF-beta-transgenic Th3 cells rescue IL-2-deficient mice from autoimmunity. J Immunol 178:172–178

    Article  CAS  PubMed  Google Scholar 

  107. Viglietta V, Baecher-Allan C, Weiner HL, Hafler DA (2004) Loss of functional suppression by CD4+CD25+ regulatory T cells in patients with multiple sclerosis. J Exp Med 199:971–979

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Haseda F, Imagawa A, Murase-Mishiba Y, Terasaki J, Hanafusa T (2013) CD4+ CD45RA FoxP3high activated regulatory T cells are functionally impaired and related to residual insulin-secreting capacity in patients with type 1 diabetes. Clin Exp Immunol 173:207–216

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Bonelli M, Savitskaya A, von Dalwigk K, Steiner CW, Aletaha D, Smolen JS, Scheinecker C (2008) Quantitative and qualitative deficiencies of regulatory T cells in patients with systemic lupus erythematosus (SLE). Int Immunol 20:861–868

    Article  CAS  PubMed  Google Scholar 

  110. van Roon JAG, Hartgring SAY, van der Wurff-Jacobs KMG, Bijlsma JWJ, Lafeber FPJG (2010) Numbers of CD25+Foxp3+ T cells that lack the IL-7 receptor are increased intra-articularly and have impaired suppressive function in RA patients. Rheumatology (Oxford) 49:2084–2089

    Article  PubMed  Google Scholar 

  111. Thiruppathi M, Rowin J, Li Jiang Q, Sheng JR, Prabhakar BS, Meriggioli MN (2012) Functional defect in regulatory T cells in myasthenia gravis. Ann N Y Acad Sci 1274:68–76

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Smigiel KS, Srivastava S, Stolley JM, Campbell DJ (2014) Regulatory T-cell homeostasis: steady-state maintenance and modulation during inflammation. Immunol Rev 259:40–59

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Arpaia N, Green JA, Moltedo B, Arvey A, Hemmers S, Yuan S, Treuting PM, Rudensky AY (2015) A distinct function of regulatory T cells in tissue protection. Cell 162:1078–1089

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Kanamori M, Nakatsukasa H, Okada M, Lu Q, Yoshimura A (2016) Induced regulatory T cells: their development, stability, and applications. Trends Immunol 37:803–811

    Article  CAS  PubMed  Google Scholar 

  115. Qureshi OS, Zheng Y, Nakamura K, Attridge K, Manzotti C, Schmidt EM, Baker J, Jeffery LE, Kaur S, Briggs Z, Hou TZ, Futter CE, Anderson G, Walker LSK, Sansom DM (2011) Trans-endocytosis of CD80 and CD86: a molecular basis for the cell-extrinsic function of CTLA-4. Science 332:600–603

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Onishi Y, Fehervari Z, Yamaguchi T, Sakaguchi S (2008) Foxp3+ natural regulatory T cells preferentially form aggregates on dendritic cells in vitro and actively inhibit their maturation. Proc Natl Acad Sci U S A 105:10113–10118

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Yan Z, Garg SK, Banerjee R (2010) Regulatory T cells interfere with glutathione metabolism in dendritic cells and T cells. J Biol Chem 285:41525–41532

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Akkaya B, Oya Y, Akkaya M, Al Souz J, Holstein AH, Kamenyeva O, Kabat J, Matsumura R, Dorward DW, Glass DD, Shevach EM (2019) Regulatory T cells mediate specific suppression by depleting peptide-MHC class II from dendritic cells. Nat Immunol 20:218–231

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Liang B, Workman C, Lee J, Chew C, Dale BM, Colonna L, Flores M, Li N, Schweighoffer E, Greenberg S, Tybulewicz V, Vignali D, Clynes R (2008) Regulatory T cells inhibit dendritic cells by lymphocyte activation gene-3 engagement of MHC class II. J Immunol 180:5916–5926

    Article  CAS  PubMed  Google Scholar 

  120. Rubtsov YP, Rasmussen JP, Chi EY, Fontenot J, Castelli L, Ye X, Treuting P, Siewe L, Roers A, Henderson WR, Muller W, Rudensky AY (2008) Regulatory T cell-derived interleukin-10 limits inflammation at environmental interfaces. Immunity 28:546–558

    Article  CAS  PubMed  Google Scholar 

  121. Chaudhry A, Samstein RM, Treuting P, Liang Y, Pils MC, Heinrich J-M, Jack RS, Wunderlich FT, Brüning JC, Müller W, Rudensky AY (2011) Interleukin-10 signaling in regulatory T cells is required for suppression of Th17 cell-mediated inflammation. Immunity 34:566–578

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Freuchet A, Salama A, Bézie S, Tesson L, Rémy S, Humeau R, Règue H, Sérazin C, Flippe L, Peterson P, Vimond N, Usal C, Ménoret S, Heslan J-M, Duteille F, Blanchard F, Giral M, Colonna M, Anegon I, Guillonneau C (2022) IL-34 deficiency impairs FOXP3+ Treg function in a model of autoimmune colitis and decreases immune tolerance homeostasis. Clin Transl Med 12:e988

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Guillonneau C, Bézie S, Anegon I (2017) Immunoregulatory properties of the cytokine IL-34. Cell Mol Life Sci 74:2569–2586

    Article  CAS  PubMed  Google Scholar 

  124. Collison LW, Workman CJ, Kuo TT, Boyd K, Wang Y, Vignali KM, Cross R, Sehy D, Blumberg RS, Vignali DAA (2007) The inhibitory cytokine IL-35 contributes to regulatory T-cell function. Nature 450:566–569

    Article  CAS  PubMed  Google Scholar 

  125. Spolski R, Li P, Leonard WJ (2018) Biology and regulation of IL-2: from molecular mechanisms to human therapy. Nat Rev Immunol 18:648–659

    Article  CAS  PubMed  Google Scholar 

  126. Wong HS, Park K, Gola A, Baptista AP, Miller CH, Deep D, Lou M, Boyd LF, Rudensky AY, Savage PA, Altan-Bonnet G, Tsang JS, Germain RN (2021) A local regulatory T cell feedback circuit maintains immune homeostasis by pruning self-activated T cells. Cell 184:3981–3997.e22

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Sauer AV, Brigida I, Carriglio N, Hernandez RJ, Scaramuzza S, Clavenna D, Sanvito F, Poliani PL, Gagliani N, Carlucci F, Tabucchi A, Roncarolo MG, Traggiai E, Villa A, Aiuti A (2012) Alterations in the adenosine metabolism and CD39/CD73 adenosinergic machinery cause loss of Treg cell function and autoimmunity in ADA-deficient SCID. Blood 119:1428–1439

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Regateiro FS, Cobbold SP, Waldmann H (2013) CD73 and adenosine generation in the creation of regulatory microenvironments. Clin Exp Immunol 171:1–7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

This study was supported by the National Natural Science Foundation of China (82022019, 82101414).

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Wu, C., Jiang, ML., Pang, T., Zhang, CJ. (2024). T Cell Subsets and Immune Homeostasis. In: Kumar, V. (eds) Immune Homeostasis. Methods in Molecular Biology, vol 2782. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-3754-8_3

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