Multi-tasking of Helper T Cells

Overview

Journal Immunology

Specialty Allergy & Immunology

Date 2010 Jun 19

PMID 20557575

Citations 67

Authors

Yisong Y Wan

Affiliations

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Abstract

CD4 T helper cells (Th) are critical in combating pathogens and maintaining immune homeostasis. Since the establishment of the Th1-Th2 paradigm in the 1980s, many types of specialized Th cells, including Th1, Th2, Th17, Th9, follicular helper T and regulatory T, have been identified. We have become accustomed to the idea that different Th cells are 'committed' to their paths but recent emerging evidence suggests that under certain conditions, seemingly committed Th cells possess plasticity and may convert into other types of effector cells. In this review, we will first introduce the major sub-types of Th cells that are involved in immune regulation. Then, we will describe in detail the inter-convertibility of Th cells among different sub-types under in vitro and in vivo conditions. Finally, we will discuss our current understanding of the underlying mechanisms on how a particular type of Th cells may convert into other types of Th cells.

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References

Tsuji M, Komatsu N, Kawamoto S, Suzuki K, Kanagawa O, Honjo T . Preferential generation of follicular B helper T cells from Foxp3+ T cells in gut Peyer's patches. Science. 2009; 323(5920):1488-92. DOI: 10.1126/science.1169152. View

Shi G, Cox C, Vistica B, Tan C, Wawrousek E, Gery I . Phenotype switching by inflammation-inducing polarized Th17 cells, but not by Th1 cells. J Immunol. 2008; 181(10):7205-13. PMC: 2665021. DOI: 10.4049/jimmunol.181.10.7205. View

Davidson N, Leach M, Fort M, Thompson-Snipes L, Kuhn R, Muller W . T helper cell 1-type CD4+ T cells, but not B cells, mediate colitis in interleukin 10-deficient mice. J Exp Med. 1996; 184(1):241-51. PMC: 2192682. DOI: 10.1084/jem.184.1.241. View

Wilson C, Rowell E, Sekimata M . Epigenetic control of T-helper-cell differentiation. Nat Rev Immunol. 2009; 9(2):91-105. DOI: 10.1038/nri2487. View

Wan Y, Flavell R . Regulatory T-cell functions are subverted and converted owing to attenuated Foxp3 expression. Nature. 2007; 445(7129):766-70. DOI: 10.1038/nature05479. View

Harrington L, Janowski K, Oliver J, Zajac A, Weaver C . Memory CD4 T cells emerge from effector T-cell progenitors. Nature. 2008; 452(7185):356-60. DOI: 10.1038/nature06672. View

Bending D, De La Pena H, Veldhoen M, Phillips J, Uyttenhove C, Stockinger B . Highly purified Th17 cells from BDC2.5NOD mice convert into Th1-like cells in NOD/SCID recipient mice. J Clin Invest. 2009; 119(3):565-72. PMC: 2648686. DOI: 10.1172/JCI37865. View

Swihart K, Fruth U, Messmer N, Hug K, BEHIN R, Huang S . Mice from a genetically resistant background lacking the interferon gamma receptor are susceptible to infection with Leishmania major but mount a polarized T helper cell 1-type CD4+ T cell response. J Exp Med. 1995; 181(3):961-71. PMC: 2191906. DOI: 10.1084/jem.181.3.961. View

Leung B, McInnes I, Esfandiari E, Wei X, Liew F . Combined effects of IL-12 and IL-18 on the induction of collagen-induced arthritis. J Immunol. 2000; 164(12):6495-502. DOI: 10.4049/jimmunol.164.12.6495. View

10.

Robinson D, Hamid Q, Ying S, Tsicopoulos A, Barkans J, Bentley A . Predominant TH2-like bronchoalveolar T-lymphocyte population in atopic asthma. N Engl J Med. 1992; 326(5):298-304. DOI: 10.1056/NEJM199201303260504. View

11.

Nurieva R, Chung Y, Hwang D, Yang X, Kang H, Ma L . Generation of T follicular helper cells is mediated by interleukin-21 but independent of T helper 1, 2, or 17 cell lineages. Immunity. 2008; 29(1):138-49. PMC: 2556461. DOI: 10.1016/j.immuni.2008.05.009. View

12.

Veldhoen M, Uyttenhove C, Van Snick J, Helmby H, Westendorf A, Buer J . Transforming growth factor-beta 'reprograms' the differentiation of T helper 2 cells and promotes an interleukin 9-producing subset. Nat Immunol. 2008; 9(12):1341-6. DOI: 10.1038/ni.1659. View

13.

Parronchi P, Macchia D, Piccinni M, Biswas P, Simonelli C, Maggi E . Allergen- and bacterial antigen-specific T-cell clones established from atopic donors show a different profile of cytokine production. Proc Natl Acad Sci U S A. 1991; 88(10):4538-42. PMC: 51696. DOI: 10.1073/pnas.88.10.4538. View

14.

Bettelli E, Carrier Y, Gao W, Korn T, Strom T, Oukka M . Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature. 2006; 441(7090):235-8. DOI: 10.1038/nature04753. View

15.

Wenner C, Guler M, Macatonia S, OGarra A, Murphy K . Roles of IFN-gamma and IFN-alpha in IL-12-induced T helper cell-1 development. J Immunol. 1996; 156(4):1442-7. View

16.

Provoost S, Maes T, Van Durme Y, Gevaert P, Bachert C, Schmidt-Weber C . Decreased FOXP3 protein expression in patients with asthma. Allergy. 2009; 64(10):1539-1546. DOI: 10.1111/j.1398-9995.2009.02056.x. View

17.

Ouyang W, Ranganath S, Weindel K, Bhattacharya D, MURPHY T, Sha W . Inhibition of Th1 development mediated by GATA-3 through an IL-4-independent mechanism. Immunity. 1998; 9(5):745-55. DOI: 10.1016/s1074-7613(00)80671-8. View

18.

Zhou X, Bailey-Bucktrout S, Jeker L, Penaranda C, Martinez-Llordella M, Ashby M . Instability of the transcription factor Foxp3 leads to the generation of pathogenic memory T cells in vivo. Nat Immunol. 2009; 10(9):1000-7. PMC: 2729804. DOI: 10.1038/ni.1774. View

19.

Shimoda K, van Deursen J, Sangster M, Sarawar S, Carson R, Tripp R . Lack of IL-4-induced Th2 response and IgE class switching in mice with disrupted Stat6 gene. Nature. 1996; 380(6575):630-3. DOI: 10.1038/380630a0. View

20.

Joetham A, Matsubara S, Okamoto M, Takeda K, Miyahara N, Dakhama A . Plasticity of regulatory T cells: subversion of suppressive function and conversion to enhancement of lung allergic responses. J Immunol. 2008; 180(11):7117-24. DOI: 10.4049/jimmunol.180.11.7117. View