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  • Title: Inducible costimulator (ICOS) is a marker for highly suppressive antigen-specific T cells sharing features of TH17/TH1 and regulatory T cells.
    Author: Vocanson M, Rozieres A, Hennino A, Poyet G, Gaillard V, Renaudineau S, Achachi A, Benetiere J, Kaiserlian D, Dubois B, Nicolas JF.
    Journal: J Allergy Clin Immunol; 2010 Aug; 126(2):280-9, 289.e1-7. PubMed ID: 20624644.
    Abstract:
    BACKGROUND: CD4(+)CD25(+) regulatory T (Treg) cells are involved in the downmodulation of numerous immune responses to pathogens, tumors, or allergens. OBJECTIVE: In this study, we further characterized the nature of Treg cells that control skin inflammatory reactions to haptens. METHODS: In a model of contact hypersensitivity to 2,4-dinitro-fluorobenzene, we have investigated the phenotype, the specificity, and the origin of Treg cells that modulate the priming of effector CD8(+) T cells responsible for the development of the pathology. RESULTS: 2,4-Dinitrofluorobenzene immunization induced a population of CD4(+)CD25(+) Treg cells that controlled CD8(+) T-cell effector responses in a hapten-specific manner in vivo. High levels of inducible costimulator (ICOS) expression defined a population of CD4(+)CD25(+)FoxP3(+) (forkhead box protein 3) Treg cells that presented superior suppressive activity. Importantly, ICOS(+) Treg cells were distinguishable from all other FoxP3(+) Treg cells by the expression of IL-10, IL-17, and IFN-gamma. Hapten-specific Treg cells proliferating in response to their cognate antigen in vivo predominantly displayed a CD25(+)FoxP3(+)ICOS(+) phenotype. By using reporter mice, we showed that ICOS(+) Treg cells derived from the expansion of natural CD4(+)FoxP3(+) Treg cells rather than generation of adaptive Treg cells. Furthermore, the generation of ICOS(+) Treg cells depended on innate cells rather than the effector CD8(+) T-cell population. CONCLUSION: Taken together, our data show that a population of CD4(+)CD25(+)FoxP3(+) T cells upregulates ICOS on in vivo sensitization and specifically suppresses hapten-reactive CD8(+) T cells both in vivo and in vitro.
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