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Prepublished online as a Blood First Edition Paper on July 3, 2003; DOI 10.1182/blood-2003-01-0100. This Article Full Text (PDF) All Versions of this Article: 2003-01-0100v1 102/8/2933    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Bernabei, P. Articles by Novelli, F. Search for Related Content PubMed PubMed Citation Articles by Bernabei, P. Articles by Novelli, F. Social Bookmarking                   What's this? Submitted January 13, 2003 Accepted June 23, 2003 IGF-1 down-regulates IFN-R2 chain surface expression and desensitizes IFN-/STAT-1 signaling in human T lymphocytes Paola Bernabei, Marita Bosticardo, Giuliana Losana, Gabriella Regis, Francesca Di Paola, Stefania De Angelis, Mirella Giovarelli, and Francesco Novelli* Center for Experimental Research and Medical Studies (CeRMS), San Giovanni Battista Hospital - Molinette, Turin, Italy; Department of Clinical and Biological Sciences, San Luigi Gonzaga Hospital, University of Turin, Turin, Italy * Corresponding author; email: franco.novelli{at}unito.it. The 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. 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