Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• European journal of immunology, 2006-10, Vol.36 (10), p.2601-2612

Ort / Verlag

Weinheim: WILEY‐VCH Verlag

Erscheinungsjahr

2006

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.