/STAT-1 signaling in human T lymphocytes γ desensitizes IFN- R2 chain surface expression and γ IGF-1 down-regulates IFN-

AbstractThe ability of IGF-1 to regulate surface expression of the IFN- R2 transducing chain and activation of IFN- -induced-STAT-1 in human T cells was analyzed. We show that, especially in the absence of serum (which contains IGF-1), IGF-1 down-regulated surface expression of the IFN- R2 chain and inhibited both IFN- -dependent-STAT-1 activation and apoptosis in T cell lines ST4, Jurkat and Molt-4. IFN- R2 down-regulation resulted from its enhanced internalization since IGF-1 completely restored the uptake of anti-IFN- R2 mAb in serum-deprived T cell lines. When the interaction between IGF-1 and its receptor was blocked by anti-IGF-1R mAb, enhancement of IFN- R2 surface expression, STAT-1 activation and reinstatement of IFN- -induced apoptosis were observed. Enhanced expression of IFN- R2 was also observed in PHA-activated T lymphoblasts cultured in the presence of anti-IGF-1R mAb, whereas IGF-1 or anti-IGF-1R mAb did not modify the high IFN- R2 expression in B and myeloid cell lines. Both IGF-1 and anti-IGF-1R mAb did not modify the constitutive expression of IFN- R2 mRNA in T cells as well as the high IFN- R1 binding chain surface expression in T, B and myeloid cells. These data indicate that IGF-1 plays a critical role in the desensitization of IFN- /STAT-1 signaling in T lymphocytes by delivering a signal for IFN- R2 internalization.From bloodjournal.hematologylibrary.org by guest on June 5, 2013. For personal use only.