Abstract
CD4 helper T (Th)-cells and the cytokines that they produce play essential regulatory roles in immune and autoimmune responses. Th activation and differentiation is regulated by costimulatory receptors. CD28 and CTLA-4 are important in maintaining the threshold of T-cell activation. ICOS and PD-1 are novel costimulatory receptors expressed on activated T-cells. B7-H3 recognizes a putative costimulatory receptor on activated T-cells. Here we summarize the latest developments in the novel costimulatory molecules and their roles in regulating Th activation, differentiation, and function.
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References
Dong C, Flavell RA: Cell fate decision: T-helper 1 and 2 subsets in immune responses. Arthritis Res 2000; 2:179–188.
Glimcher LH, Murphy KM: Lineage commitment in the immune system: the T helper lymphocyte grows up. Genes Dev 2000;14:1693–1711.
Lenschow DJ, Walunas TL, Bluestone JA: CD28/B7 system of T cell costimulation. Annu Rev Immunol 1996; 14:233–258.
Chambers CA, Allison JP: Costimulatory regulation of T cell function. Curr Opin Cell Biol 1999;11: 203–210.
Hutloff A, Dittrich AM, Beier KC, et al.: ICOS is an inducible T-cell co-stimulator structurally and functionally related to CD28. Nature 1999;397:263–266.
Yoshinaga SK, Whoriskey JS, Khare SP, et al.: T-cell co-stimulation through B7RP-1 and ICOS. Nature 1999;402:827–832.
Coyle AJ, Lehar S, Lloyd C, et al.: The CD28-related molecule ICOS is required for effective t cell-dependent immune responses. Immunity 2000;13:95–105.
Swallow MM, Wallin JJ, Sha WC: B 7 h, a novel costimulatory homolog of B7.1 and B7.2, is induced by TNFa. Immunity 1999;11:423–432.
Wallin JJ, Liang L, Bakardjiev A, et al.: Enhancement of CD8+ T cell responses by 1COS/B:7 h costimulation. J Immunol 2001;167(1):132–139.
Liu X, Bai XF, Gao JX, et al.: B7H costimulates clonal expansion of, and cognate destruction of tumor cells by, CD8(+) T lymphocytes in vivo. J Exp Med 2001; 194:1339–1348.
Dong C, Juedes AE, Termann UA, et al.: ICOS co-stimulatory receptor is essential for T-cell activation and function. Nature 2001;409:97–102.
Tafuri A, Shahinian A, Bladt F, et al.: ICOS is essential for effective T-helper-cell responses. Nature 2001; 409:105–109.
Ho IC, Lo D, Glimcher LH: c-maf promotes T helper cell type 2 (Th2) and attenuates Th1 differentiation by both interleukin 4-dependent and-independent mechanisms. J Exp Med 1998;188:1859–1866.
Kim JI, Ho IC, Grusby MJ, et al.: The transcription factor c-Maf controls: the production of interleukin-4 but not other Th2 cytokines. Immunity 1999;10:745–751.
McAdam AJ, Greenwald RF, Levin MA, et al.: ICOS is critical for CD40-mediated antibody class switching. Nature 2001;409:102–105.
Dong C, Temann UA, Flavell RA: Cutting edge: critical role of inducible costimulator in germinal center reactions. Immunol 2001:166:3659–3662.
Juedes AE, Hjelmstrom P, Bergman CM, et al.: Kinetics and cellular origin of cytokines in the central nervous system: insight into mechanisms of myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis. J Immunol 2000;164:419–426.
Suen WE, Begman CM, Hejelmstrom P, et al: A critical role for lymphotoxin in experimental allergic encephalomyelitis. J Exp Med 1997;186:1233–1240.
Oliveira-dos-Santos AJ, Ho A, Tada Y, et al.: CD28 costimulation is crucial for the development of spontaneous auto-immune encephalomyelitis. J Immunol 1999;162: 4490–4495.
Girvin AM, DalCanto MC, Rhee L, et al.: A critical role for B7/CD28 costimulation in experimental autoimmune encephalomyelitis: a comparative study using costimulatory molecule-deficient mice and monoclonal antibody blockade. J Immunol 2000;164:136–143.
Chang TT, Jabs C, Sobel RA, et al.: Studies in B7-deficient mice reveal a critical role for B7 costimulation in both induction and effector phases of experimental autoimmune encephalomyelitis. J Exp Med 1999; 190:733–740.
Rottman JB, Smith T, Tonra JR, et al.: The costimulatory molecule ICOS plays an important role in the immunopathogenesis of EAE. Nat Immunol 2001; 2:605–611.
Chapoval AI, Ni J, Lau JS, et al.: B7-H3: a costimulatory molecule for T cell activation and IFN-gamma production. Nat Immunol 2001;2:269–274.
Sun M, Richards S, Prasad DVR, et al.: Characterization of mouse and human B7-H3 genes. J Immunol 2002;168:6294–6297.
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Dong, C., Nurieva, R.I. & Prasad, D.V.R. Immune regulation by novel costimulatory molecules. Immunol Res 28, 39–48 (2003). https://doi.org/10.1385/IR:28:1:39
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DOI: https://doi.org/10.1385/IR:28:1:39