ICOS cooperates with CD28, IL-2 and IFN-γ and modulates activation of human naïve CD4+ T cells

Riccardo Mesturini, Stefania Nicola, Annalisa Chiocchetti, Ilaria Seren Bernardone, Luca Castelli, Thea Bensi, Massimo Ferretti, Cristoforo Comi, Chen Dong, Josè Maria Rojo, Junji Yagi, Umberto Dianzani

Risultato della ricerca: Contributo su rivistaArticolo in rivistapeer review

Abstract

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.

Lingua originaleInglese
pagine (da-a)2601-2612
Numero di pagine12
RivistaEuropean Journal of Immunology
Volume36
Numero di pubblicazione10
DOI
Stato di pubblicazionePubblicato - ott 2006

Fingerprint

Entra nei temi di ricerca di 'ICOS cooperates with CD28, IL-2 and IFN-γ and modulates activation of human naïve CD4+ T cells'. Insieme formano una fingerprint unica.

Cita questo