期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 36, 期 10, 页码 2601-2612出版社
WILEY
DOI: 10.1002/eji.200535571
关键词
costimulatory molecules; naive cells; regulatory T cells
类别
资金
- Telethon [GGP04071] Funding Source: Medline
Several sets of data indicate that ICOS regulates cytokine production in activated T cells, but is less effective on naive T cells. This work evaluates ICOS function in human naive CD4(+) T cells through an assessment of the effect of soluble forms of the ICOS and CD28 physiological ligands on activation driven by anti-CD3 mAb. ICOS strikingly potentiated secretion of IL-2, IFN-gamma, IL-10, and TNF-alpha, but not IL-4, promoted by optimal stimulation of CD3+CD28, and it was the key switching-factor of activation when cells received suboptimal stimulation of CD3+CD28 or stimulation of CD3 alone in the presence of exogenous IL-2. In these conditions, blockade of IL-2 and IFN-gamma showed that ICOS builds up a positive feedback loop with IFN-gamma, which required IL-2 and was inhibited by IL-4. By contrast, in the absence of CD28 triggering or exogenous IL-2, ICOS-induced costimulation mainly supported expression of TGF-beta 1 and FoxP3 and differentiation of regulatory T cells capable to inhibit proliferation of naive CD4(+) T cells driven by allogeneic cells. These data suggest that ICOS favors differentiation of Th effector cells when cooperates with appropriate activation stimuli such as CD3 + CD28 or CD3 + IL-2, whereas it supports differentiation of regulatory T cells when costimulatory signals are insufficient.
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