TY - JOUR
T1 - ICOS cooperates with CD28, IL-2 and IFN-γ and modulates activation of human naïve CD4+ T cells
AU - Mesturini, Riccardo
AU - Nicola, Stefania
AU - Chiocchetti, Annalisa
AU - Bernardone, Ilaria Seren
AU - Castelli, Luca
AU - Bensi, Thea
AU - Ferretti, Massimo
AU - Comi, Cristoforo
AU - Dong, Chen
AU - Rojo, Josè Maria
AU - Yagi, Junji
AU - Dianzani, Umberto
PY - 2006/10
Y1 - 2006/10
N2 - 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.
AB - 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.
KW - Costimulatory molecules
KW - Naïve cells
KW - Regulatory T cells
UR - http://www.scopus.com/inward/record.url?scp=33750256934&partnerID=8YFLogxK
U2 - 10.1002/eji.200535571
DO - 10.1002/eji.200535571
M3 - Article
SN - 0014-2980
VL - 36
SP - 2601
EP - 2612
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 10
ER -