IFN-α exerts opposing effects on activation-induced and IL-7-induced proliferation of T cells that may impair homeostatic maintenance of CD4+T cell numbers in treated HIV infection

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)
205 Downloads (Pure)

Abstract

To 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.
Original languageEnglish
Pages (from-to)2178-2186
JournalJournal of Immunology
Volume193
Issue number5
Early online date25 Jul 2014
DOIs
Publication statusPublished - 1 Sep 2014

Fingerprint

Dive into the research topics of 'IFN-α exerts opposing effects on activation-induced and IL-7-induced proliferation of T cells that may impair homeostatic maintenance of CD4+T cell numbers in treated HIV infection'. Together they form a unique fingerprint.

Cite this