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http://dx.doi.org/10.4110/in.2011.11.6.336

T Cell Receptor Signaling That Regulates the Development of Intrathymic Natural Regulatory T Cells  

Song, Ki-Duk (Center for Agricultural Biomaterials, Seoul National University)
Hwang, Su-Jin (Program on Genomics of Differentiation, Eunice Shriver National Institute of Child Health and Human Development, National Institutes of Health)
Yun, Cheol-Heui (Center for Agricultural Biomaterials, Seoul National University)
Publication Information
IMMUNE NETWORK / v.11, no.6, 2011 , pp. 336-341 More about this Journal
Abstract
T cell receptor (TCR) signaling plays a critical role in T cell development, survival and differentiation. In the thymus, quantitative and/or qualitative differences in TCR signaling determine the fate of developing thymocytes and lead to positive and negative selection. Recently, it has been suggested that self-reactive T cells, escape from negative selection, should be suppressed in the periphery by regulatory T cells (Tregs) expressing Foxp3 transcription factor. Foxp3 is a master factor that is critical for not only development and survival but also suppressive activity of Treg. However, signals that determine Treg fate are not completely understood. The availability of mutant mice which harbor mutations in TCR signaling mediators will certainly allow to delineate signaling events that control intrathymic (natural) Treg (nTreg) development. Thus, we summarize the recent progress on the role of TCR signaling cascade components in nTreg development from the studies with murine model.
Keywords
T cell receptor; nTreg; Intrathymic selection;
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1 Zuniga-Pflucker JC, Jones LA, Chin LT, Kruisbeek AM: CD4 and CD8 act as co-receptors during thymic selection of the T cell repertoire. Semin Immunol. 3:167-175, 1991
2 Sakaguchi S, Fukuma K, Kuribayashi K, Masuda T: Organ-specific autoimmune diseases induced in mice by elimination of T cell subset. I. Evidence for the active participation of T cells in natural self-tolerance; deficit of a T cell subset as a possible cause of autoimmune disease. J Exp Med 161;72-87, 1985.   DOI   ScienceOn
3 Kim JM, Rasmussen JP, Rudenky AY: Regulatory T cells prevent catastrophic autoimmunity throughout the life span. Nature Immunol 8;191-197, 2007.   DOI   ScienceOn
4 Sauer S, Bruno L, Hertweck A, Finlay D, Leleu M, Spivakov M, Knight ZA, Cobb BS, Cantrell D, O'Connor E, Shokat KM, Fisher AG, Merkenschlager M: T cell receptor signaling controls Foxp3 expression via PI3K, Akt, and mTOR. Proc Natl Acad Sci USA 105;7797-7802, 2008.   DOI   ScienceOn
5 Starr TK, Jameson SC, Hogquist KA: Positive and negative selection of T cells. Annu Rev Immunol 21;139-176, 2002.
6 Au-Yeung BB, Deindl S, Hsu LY, Palacios EH, Levin SE, Kuriyan J, Weiss A: The structure, regulation, and function of ZAP-70. Immunol Rev 228;41-57, 2009   DOI   ScienceOn
7 Samelson LE: Signal transduction mediated by the T cell antigen receptor: the role of adapter proteins. Annu Rev Immunol 20;371-394, 2002.   DOI   ScienceOn
8 Sommers CL, Samelson LE, Love PE: LAT: a T lymphocyte adapter protein that couples the antigen receptor to downstream signaling pathways. Bioessays 26;61-67, 2004.   DOI   ScienceOn
9 Fuller DM, Zhu M, Ou-Yang CW, Sullivan SA, Zhang W: A tale of two TRAPs: LAT and LAB in the regulation of lymphocyte development, activation, and autoimmunity. Immunol Res 49;97-108, 2011.   DOI
10 Wange RL: LAT, the linker for activation of T cells: a bridge between T cell-specific and general signaling pathways. Sci STIKE 2000 63;re1, 2000.
11 Hsu LY, Tan YX, Xiao Z, Malissen M, Weiss A: A hypomorphic allele of ZAP-70 reveals a distinct thymic threshold for autoimmune disease versus autoimmune reactivity. J Exp Med 206;2527-2541, 2009.   DOI   ScienceOn
12 Burchill MA, Yang J, Vang KB, Moon JJ, Chu HH, Lio CW, Vegoe AL, Hsieh CS, Jenkins MK, Farrar MA: Linked T cell receptor and cytokine signaling govern the development of the regulatory T cell repertoire. Immunity 28;112-121, 2008.   DOI   ScienceOn
13 Lio CW, Hsieh CS: A two-step process for thymic regulatory T cell development. Immunity 28;100-111, 2008.   DOI   ScienceOn
14 Cheng G, Yu A, Malek TR: T-cell tolerance and the multi-functional role of IL-2R signaling in T-regulatory cells. Immunol Rev 241;63-76, 2011.   DOI   ScienceOn
15 Bensinger SJ, Bandeira A, Jordan MS, Caton AJ, Laufer TM: Major histocompatibility complex class II-positive cortical epithelium mediates the selection of CD4+25+ immunoregulatory T cells. J Exp Med 194;427-438, 2001.   DOI   ScienceOn
16 Fontenot JD, Dooley JL, Farr AG, Rudensky AY: Developmental regulation of Foxp3 expression during ontogeny. J Exp Med 202;901-916, 2005.   DOI   ScienceOn
17 Tai X, Cowan M, Feigenbaum L, Singer A: CD28 costimulation of developing thymocytes induces Foxp3 expression and regulatory T cell differentiation independently of interleukin 2. Nat Immunol 6;152-162, 2005.   DOI   ScienceOn
18 Samelson LE: Signal transduction mediated by the T cell antigen receptor: the role of adapter proteins. Annu Rev Immunol 20; 371-394, 2002.   DOI   ScienceOn
19 Ho SN, Thomas DJ, Timmerman LA, Li X, Francke U, Crabtree GR: NFATc3, a lymphoid-specific NFATc family member that is calcium-regulated and exhibits distinct DNA binding specificity. J Biol Chem 270;19898-19907, 1995.   DOI
20 Michie AM, Zúñiga-Pflücker JC: Regulation of thymocyte differentiation: pre-TCR signals and beta-selection. Semin Immunol 14;311-323, 2002.   DOI   ScienceOn
21 Ellmeier W, Sawada S, Littman DR: The regulation of CD4 and CD8 coreceptor gene expression during T cell development. Annu Rev Immunol 17;523-554, 1999   DOI   ScienceOn
22 Werlen G, Hausmann B, Naeher D, Palmer E: Signaling life and death in the thymus: timing is everything. Science 299;1859-1863, 2003.   DOI
23 Gascoigne NR, Palmer E: Signaling in thymic selection. Curr Opin Immunol 23;207-212, 2011.   DOI   ScienceOn
24 Fu G, Chen Y, Yu M, Podd A, Schuman J, He Y, Di L, Yassai M, Haribhai D, North PE, Gorski J, Williams CB, Wang D, Wen R: Phospholipase C$\gamma$1 is essential for T cell development, activation, and tolerance. J Exp Med 207;309-318, 2010.   DOI   ScienceOn
25 Chen X, Priatel JJ, Chow MT, Teh HS: Preferential development of CD4 and CD8 T regulatory cells in RasGRP1-deficient mice. J Immunol 180;5973-5982, 2008.   DOI
26 Tarakhovsky A, Kanner SB, Hombach J, Ledbetter JA, M$\ddot{u}$ller W, Killeen N, Rajewsky K: A role for CD5 in TCR-mediated signal transduction and thymocyte selection. Science 269;535-537, 1995   DOI
27 Ordo$\tilde{n}$ez-Rueda D, Lozano F, Sarukhan A, Raman C, Garcia- Zepeda EA, Soldevila G: Increased numbers of thymic and peripheral CD4+ CD25+Foxp3+ cells in the absence of CD5 signaling. Eur J Immunol 39;2233-2247, 2009.   DOI   ScienceOn
28 Turner M, Billadeau DD: VAV proteins as signal integrators for multi-subunit immune-recognition receptors. Nat Rev Immunol 2;476-486, 2002.   DOI
29 Tybulewicz VL: Vav-family proteins in T-cell signalling. Curr Opin Immunol 17;267-274, 2005.   DOI   ScienceOn
30 Colacios C, Casemayou A, Dejean AS, Gaits-Iacovoni F, Pedros C, Bernard I, Lagrange D, Deckert M, Lamouroux L, Jagodic M, Olsson T, Liblau RS, Fournie GJ, Saoudi A: The p.Arg63Trp polymorphism controls Vav1 functions and Foxp3 regulatory T cell development. J Exp Med 208;2183-2191, 2011.   DOI   ScienceOn
31 Tanaka S, Maeda S, Hashimoto M, Fujimori C, Ito Y, Teradaira S, Hirota K, Yoshitomi H, Katakai T, Shimizu A, Nomura T, Sakaguchi N, Sakaguchi S: Graded attenuation of TCR signaling elicits distinct autoimmune diseases by altering thymic T cell selection and regulatory T cell function. J Immunol 185;2295-2305, 2010.   DOI   ScienceOn
32 Sommers CL, Park CS, Lee J, Feng C, Fuller CL, Grinberg A, Hildebrand JA, Lacana E, Menon RK, Shores EW, Samelson LE, Love PE: A LAT mutation that inhibits T cell development yet induces lymphoproliferation. Science 296;2040-2043, 2002.   DOI
33 Koonpaew S, Shen S, Flowers L, Zhang W: LAT-mediated signaling in CD4+CD25+ regulatory T cell development. J Exp Med 203;119-129, 2006.   DOI   ScienceOn
34 Chuck MI, Zhu M, Shen S, Zhang W: The role of the LATPLC- gamma1 interaction in T regulatory cell function. J Immunol 184;2476-2486, 2010.   DOI   ScienceOn
35 Willoughby JE, Costello PS, Nicolas RH, Robinson NJ, Stamp G, Powrie F, Treisman R: Raf signaling but not the ERK effector SAP-1 is required for regulatory T cell development. J Immunol 179;6836-6844, 2007.   DOI
36 Wan YY, Flavell R: Identifying Foxp3-expressing suppressor cells with a bicistronic reporter. Proc Natl Acad Sci USA 102;5126-5131, 2005.   DOI   ScienceOn
37 Lio CW, Hsieh CS: Becoming self-aware: the thymic education of regulatory T cells. Curr Opin Immunol 23;213-219, 2011.   DOI   ScienceOn
38 Robey E, Fowlkes BJ: Selective events in T cell development. Annu Rev Immunol 12;675-705, 1994.   DOI   ScienceOn
39 Kim JK, Klinger M, Benjamin J, Xiao Y, Erle DJ, Littman DR, Killeen N: Impact of the TCR signal on regulatory T cell homeostasis, function, and trafficking. PLoS One 4;e6580, 2009.   DOI
40 Mamchak AA, Thien CB, Dagger SA, Lyandres J, Jiang S, Langdon WY, DeFranco AL: Unaltered negative selection and Treg development of self-reactive thymocytes in TCR transgenic Fyn-deficient mice. Eur J Immunol 40;539-547, 2010.   DOI   ScienceOn