• Lilian Cha, Emma de Jong, Martyn A French, and Sonia Fernandez.
• School of Pathology and Laboratory Medicine, University of Western Australia, Crawley, Western Australia 6009, Australia; and.
• J. Immunol. 2014 Sep 1; 193 (5): 2178-86.

AbstractTo determine whether IFN-α is a cause of the T cell hyperactivation and IL-7 signaling pathway defects that are observed in some HIV patients receiving antiretroviral therapy, we have investigated the effect of IFN-α on the proliferation of CD4(+) and CD8(+) T cells from healthy donors (n = 30) and treated HIV(+) donors (n = 20). PBMC were cultured for 7 d with staphylococcal enterotoxin B or IL-7 in the absence or presence of 100 U/ml IFN-α8. Total and naive CD4(+) and CD8(+) T cells were assessed for proliferation (via Ki67 expression), CD127 expression, and phosphorylated STAT5 levels using flow cytometry. IFN-α significantly enhanced activation-induced proliferation (via staphylococcal enterotoxin B stimulation) but inhibited homeostatic proliferation (IL-7 induced) of CD4(+) and CD8(+) T cells. Both of these effects may adversely affect CD4(+) T cell homeostasis in HIV patients. CD127 expression was increased in both healthy and HIV(+) donors following culture with IFN-α8, and levels of IL-7-induced phosphorylated STAT5 were increased by IFN-α8 in healthy donors only. Hence, the inhibitory effects of IFN-α on IL-7-induced proliferation of CD4(+) T cells are unlikely to be mediated by downregulation of CD127 expression or inhibition of STAT5 phosphorylation. These data suggest that increased IFN-α activity may promote the loss of T cells by accelerating cell turnover and activation-induced cell death while decreasing the renewal of T cells by inhibiting the proliferative effect of IL-7.Copyright © 2014 by The American Association of Immunologists, Inc.

32 keywords...

hide…