T Lymphocyte Responses: Development

Lorenzo Cosmi, Università degli Studi di Firenze, Firenze, Italia
Francesco Liotta, Università degli Studi di Firenze, Firenze, Italia
Francesco Annunziato, Università degli Studi di Firenze, Firenze, Italia

Published online: March 2010

DOI: 10.1002/9780470015902.a0001244.pub2

The function of T cells is to recognize specific ‘non-self’ antigens and to generate against them specific responses to protect the body from different diseases. In particular, a subset of T lymphocytes, named T-helper cells, produces cytokines that orchestrate the immune response, whereas another subset, named cytotoxic T cells is able to kill the pathogen-infected cells.

Two population of T-helper lymphocytes exist: T-effector cells, devoted to respond to foreign antigens and to protect the body from infection and tumours, and T-regulatory cells, whose main function is to suppress T-effector responses and to avoid the development of atoimmune diseases.

T-effector lymphocytes can be divided, according to their cytokines production profile in TH1, TH2 and TH17 cells, whereas T-regulatory cells can be distinguished, on the basis of their origin, in natural and adaptive.

Key Concepts

  • T- and B cells are the major cellular components of the adaptive immune response.
  • CD4+ T-helper lymphocytes produce cytokines that orchestrate the immune response, whereas CD8+ T cytotoxic lymphocytes kill the target cells.
  • T-helper lymphocytes can be distinguished in effector cells, which protect the body from pathogens, and regulatory T cells, that suppress effector responses, when they may become dangerous for the host.
  • Effector T-helper cells can be distinguished, according to the cytokines they are able to produce, in TH1, TH2, and TH17 cells.
  • TH1 cells play an important role in the protection against intracellular pathogens, but they could be involved in the pathogenesis of autoimmune and inflammatory disorders, when Treg cells fail to control autoreactive clones.
  • TH2 cells are mainly involved in the protection against parasitic helminths, but they also play a central role in the development of allergic disorders.
  • TH17 cells favour the clearance of extracellular pathogens, and play a pathogenic role in autoimmune and other chronic inflammatory disorders, particularly when they acquire the ability to produce IFN, thus becoming TH17/TH1 cells.
  • Treg cells can be distinguished in natural Treg cells, a population already planned to suppress the response against self-antigens since its birth in thymus, and adaptive Treg cells which acquires their suppressive activity in the periphery.

Keywords: TH1; TH2; TH17; Treg

Figure 1. Phenotypes of human effector T-helper cells.
Figure 2. Natural occurring and adaptive Treg lymphocytes in humans.
close
 References
    book Abbas AK, Litchman AH and Pober JS (eds) (1997) Cellular and Molecular Immunology. Philadelphia: W.B. Saunders Company.
    Acosta-Rodriguez EV, Napolitani G, Lanzavecchia A and Sallusto F (2007) Interleukins 1beta and 6 but not transforming growth factor-beta are essential for the differentiation of interleukin 17-producing human T helper cells. Nature Immunology 8: 942–949.
    Akira S, Takeda K and Kaisho T (2001) Toll-like receptors: critical proteins linking innate and acquired immunity. Nature Immunology 2: 675–680.
    Annunziato F, Cosmi L, Liotta F et al. (2002) Phenotype, localization, and mechanism of suppression of CD4(+)CD25(+) human thymocytes. Journal of Experimental Medicine 96: 379–387.
    Annunziato F, Cosmi L, Santarlasci V et al. (2007) Phenotypic and functional features of human Th17 cells. Journal of Experimental Medicine 204: 1849–1861.
    Asano M, Toda M, Sakaguchi N and Sakaguchi S (1996) Autoimmune disease as a consequence of developmental abnormality of a T cell subpopulation. Journal of Experimental Medicine 184: 387–396.
    Bacchetta R, Bigler M, Touraine JL et al. (1994) High levels of interleukin 10 production in vivo are associated with tolerance in SCID patients transplanted with HLA mismatched hematopoietic stem cells. Journal of Experimental Medicine 179: 493–502.
    Bending D, De La Peña H, Veldhoen M et al. (2009) Highly purified Th17 cells from BDC2.5NOD mice convert into Th1-like cells in NOD/SCID recipient mice. Journal of Clinical Investigation 119: 565–572.
    Chen Y, Kuchroo V, Inobe J, Hafler DA and Weiner HL (1994) Regulatory T cell clones induced by oral tolerance: suppression of autoimmune encephalomyelites. Science 265: 1237–1240.
    Chen Z, Laurence A and O'Shea JJ (2007) Signal transduction pathways and transcriptional regulation in the control of Th17 differentiation. Seminars in Immunology 19: 400–408.
    Chung Y, Chang SH, Martinez GJ et al. (2009) Critical regulation of early Th17 cell differentiation by interleukin-1 signaling. Immunity 30: 576–587.
    Collison LW, Workman CJ, Kuo TT et al. (2007) The inhibitory cytokine IL-35 contributes to regulatory T-cell function. Nature 450: 566–569.
    Cosmi L, De Palma R, Santarlasci V et al. (2008) Human interleukin 17-producing cells originate from a CD161+CD4+ T cell precursor. Journal Experimental Medicine 205: 1903–1916.
    Cosmi L, Liotta F, Angeli R et al. (2004) Th2 cells are less susceptible than Th1 cells to the suppressive activity of CD25+ regulatory thymocytes because of their responsiveness to different cytokines. Blood 103: 3117–3121.
    Cosmi L, Liotta F, Lazzeri E et al. (2003) Human CD8+CD25+ thymocytes share phenotypic and functional features with CD4+CD25+ regulatory thymocytes. Blood 102: 4107–4114.
    Cua DJ, Sherlock J, Chen Y et al. (2003) Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain. Nature 421: 744–748.
    Fontenot JD, Gavin MA and Rudensky AY (2003) Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nature Immunology 4: 330–336.
    Fukaura H, Kent SC, Pietrusewicz MJ et al. (1996) Induction of circulating myelin basic protein and proteolipid protein-specific transforming growth factorbeta1-secreting Th3 T cells by oral administration of myelin in multiple sclerosis patients. Journal of Clinical Investigation 98: 70–77.
    Gallimore A and Godkin A (2008) Regulatory T cells and tumour immunity: observations in mice and men. Immunology 123: 157–163.
    Gambineri E, Torgerson TR and Ochs HD (2003) Immune dysregulation, polyendocrinopathy, enteropathy, and X-linked inheritance (IPEX), a syndrome of systemic autoimmunity caused by mutations of FOXP3, a critical regulator of T-cell homeostasis. Current Opinion in Rheumatology 15: 430–435.
    Groux H, O'Garra A, Bigler M et al. (1997) A CD4+ T-cell subset inhibits antigen-specific T-cell responsesand prevents colitis. Nature 389: 737–742.
    Ivanov II, McKenzie BS, Zhou L et al. (2006) The orphan nuclear receptor RORt directs the differentiation program of proinflammatopry IL-17+ T helper cells. Cell 126: 1121–1131.
    Kassiotis G and O'Garra A (2009) Establishing the follicular helper identity. Immunity 31: 450–452.
    Korn T, Reddy J, Gao W et al. (2007) Myelin-specific regulatory T cells accumulate in the CNS but fail to control autoimmune inflammation. Nature Medicine 13: 423–431.
    Kukreja A, Cost G, Marker J et al. (2002) Multiple immuno-regulatory defects in type-1 diabetes. Journal of Clinical Investigation 109: 131–140.
    Lee YK, Turner H, Maynard CL et al. (2009) Late developmental plasticity in the T helper 17 lineage. Immunity 30: 92–107.
    Lin MT, Storer B, Martin PJ et al. (2003) Relation of an interleukin-10 promoter polymorphism to graft-versus-host disease and survival after hematopoietic-cell transplantation. New England Journal of Medicine 349: 2201–2210.
    Liotta F, Frosali F, Querci V et al. (2008) Human immature myeloid dendritic cells trigger a TH2-polarizing program via Jagged-1/Notch interaction. Journal of Allergy and Clinical Immunology 121: 1000–1005.
    Maggi E, Cosmi L, Liotta F et al. (2005) Thymic regulatory T cells. Autoimmunity Reviews 4: 579–586.
    Maggi L, Santarlasci V, Liotta F et al. (2007) Demonstration of circulating allergen-specific CD4+CD25highFoxp3+ T-regulatory cells in both nonatopic and atopic individuals. Journal of Allergy and Clinical Immunology 120: 429–436.
    Manetti R, Parronchi P, Giudizi MG et al. (1993) Natural killer cell stimulatory factor (interleukin 12 (IL-12)) induces T helper type 1 (Th1)-specific immune responses and inhibits the development of IL-4-producing Th cells. Journal of Experimental Medicine 177: 1199–1204.
    Martin-Orozco N, Chung Y, Chang SH, Wang YH and Dong C (2009) Th17 cells promote pancreatic inflammation but only induce diabetes efficiently in lymphopenic hosts after conversion into Th1 cells. European Journal of Immunology 39: 216–224.
    Mosmann TR, Cherwinski H, Bond MW, Giedlin MA and Coffman RL (1986) Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. Journal of Immunology 136: 2348–2357.
    Nakamura K, Kitani A, Fuss I et al. (2004) TGF-beta 1 plays an important role in the mechanism of CD4+CD25+ regulatory T cell activity in both humans and mice. Journal of Immunology 172: 834–842.
    Ouyang W, Koli JK and Zheng Y (2008) The biological functions of T helper 17 cell effector cytokines in inflammation. Immunity 28: 454–467.
    Ouyang W, Löhning M, Gao Z et al. (2000) Stat6-independent GATA-3 autoactivation directs IL-4-independent Th2 development and commitment. Immunity 12: 27–37.
    Owyang AM, Zaph C, Wilson EH et al. (2006) Interleukin 25 regulates type 2 cytokine-dependent immunity and limits chronic inflammation in the gastrointestinal tract. Journal of Experimental Medicine 203: 843–849.
    Romagnani S (1997) The Th1/Th2 paradigm. Immunology Today 18: 263–266.
    Roncarolo MG, Gregori S, Battaglia M et al. (2006) Interleukin-10-secreting type 1 regulatory T cells in rodents and humans. Immunological Reviews 212: 28–50.
    Sakaguchi S (2000) Regulatory T cells: key controllers of immunologic self-tolerance. Cell 101: 455–458.
    Santarlasci V, Maggi L, Capone M et al. (2009) TGF-beta indirectly favors the development of human Th17 cells by inhibiting Th1 cells. European Journal of Immunology 39: 207–215.
    Smeltz RB, Chen J, Ehrhardt R and Shevach EM (2002) Role of IFN-gamma in Th1 differentiation: IFN-gamma regulates IL-18R alpha expression by preventing the negative effects of IL-4 and by inducing/maintaining IL-12 receptor beta 2 expression. Journal of Immunology 168: 6165–6172.
    Szabo SJ, Dighe AS, Gubler U and Murphy KM (1997) Regulation of the interleukin (IL)-12R beta 2 subunit expression in developing T helper 1 (Th1) and Th2 cells. Journal of Experimental Medicine 185: 817–824.
    Usui T, Nishikomori R, Kitani A and Strober W (2003) GATA-3 suppresses Th1 development by downregulation of Stat4 and not through effects on IL-12Rbeta2 chain or T-bet. Immunity 18: 415–428.
    Usui T, Preiss JC, Kanno Y et al. (2006) T-bet regulates Th1 responses through essential effects on GATA-3 function rather than on IFNG gene acetylation and transcription. Journal of Experimental Medicine 203: 755–766.
    Wang ZY, Link H, Ljungdahl A et al. (1994) Induction of interferon-gamma, interleukin-4, and transforming growth factor-beta in rats orally tolerized against experimental autoimmune myasthenia gravis. Cellular Immunology 157: 353–368.
    Yao Z, Fanslow WC, Seldin MF et al. (1995) Herpesvirus Saimiri encodes a new cytokine, IL-17, which binds to a novel cytokine receptor. Immunity 3: 811–821.
    Zhu J, Cote-Sierra J, Guo L and Paul WE (2003) Stat5 activation plays a critical role in Th2 differentiation. Immunity 19: 739–748.
    Zhu J, Min B, Hu-Li J et al. (2004) Conditional deletion of Gata3 shows its essential function in T(H)1-T(H)2 responses. Nature Immunology 5: 1157–1165.
    Zhu J, Yamane H, Cote-Sierra J, Guo L and Paul WE (2006) GATA-3 promotes Th2 responses through three different mechanisms: induction of Th2 cytokine production, selective growth of Th2 cells and inhibition of Th1 cell-specific factors. Cell Research 16: 3–10.
 Further Reading
    Annunziato F, Cosmi L, Liotta F, Maggi E and Romagnani S (2009) Type 17 T helper cells-origins, features and possible roles in rheumatic disease. Nature Review. Rheumatology 5: 325–331.
    Liotta F, Cosmi L, Romagnani P et al. (2005) Functional features of human CD25+ regulatory thymocytes. Microbes and Infection 7: 1017–1022.
    Mosmann TR and Sad S (1996) The expanding universe of T-cell subsets: Th1, Th2 and more. Immunology Today 17: 138–146.
    Murphy KM and Reiner SL (2002) The lineage decisions of helper T cells. Nature Review. Immunology 2: 933–944.

Related Sub-Topics:

Acquired (Adaptive) Immunity | Cells of the Immune System
Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

Article Title: T Lymphocyte Responses: Development
 
How to Cite close
Cosmi, Lorenzo, Liotta, Francesco, and Annunziato, Francesco(Mar 2010) T Lymphocyte Responses: Development. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0001244.pub2]