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Título: | ICOS cooperates with CD28, IL-2, and IFN-g and modulates activation of human naïve CD4+ T cells |
Autor: | Mesturini, Riccardo; Nicola, Stefania; Chiocchetti, Annalisa; Bernardone, Ilaria Seren; Bensi, Thea; Ferretti, Massimo; Comi, Cristoforo; Dong, Chen; Rojo, José María CSIC ORCID CVN ; Yagi, Junji; Dianzani, Umberto | Palabras clave: | Costimulatory molecules Naïve cells Regulatory T cells |
Fecha de publicación: | oct-2006 | Editor: | Wiley-VCH | Citación: | European Journal of Immunology, 36 (10) : 2601-2612 (2006) | Resumen: | Several sets of data indicate that ICOS regulates cytokine production in activated T cells, but is less effective on naïve T cells. This work evaluates ICOS function in human naïve 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-γ, IL-10, and TNF-α, 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-γ showed that ICOS builds up a positive feedback loop with IFN-γ, 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-β1 and FoxP3 and differentiation of regulatory T cells capable to inhibit proliferation of naïve 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 | Descripción: | 12 páginas, 7 figuras -- PAGS nros. 2601-2612 | Versión del editor: | http://dx.doi.org/ 10.1002/eji.200535571 | URI: | http://hdl.handle.net/10261/65669 | DOI: | 10.1002/eji.200535571 | ISSN: | 0014-2980 | E-ISSN: | 1521-4141 |
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