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-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-beta1 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.
journal_name
Eur J Immunoljournal_title
European journal of immunologyauthors
Mesturini R,Nicola S,Chiocchetti A,Bernardone IS,Castelli L,Bensi T,Ferretti M,Comi C,Dong C,Rojo JM,Yagi J,Dianzani Udoi
10.1002/eji.200535571subject
Has Abstractpub_date
2006-10-01 00:00:00pages
2601-12issue
10eissn
0014-2980issn
1521-4141journal_volume
36pub_type
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