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

J Immunol. 2014 Sep 1;193(5):2178-86. doi: 10.4049/jimmunol.1302536. Epub 2014 Jul 25.


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.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / pathology
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / pathology
  • Cell Proliferation / drug effects*
  • Down-Regulation / drug effects
  • Down-Regulation / immunology
  • Female
  • HIV Infections / immunology*
  • HIV Infections / pathology
  • Humans
  • Interferon-alpha / immunology
  • Interferon-alpha / pharmacology*
  • Interleukin-7 / immunology*
  • Interleukin-7 Receptor alpha Subunit / immunology
  • Ki-67 Antigen / immunology
  • Male
  • Middle Aged
  • STAT5 Transcription Factor / immunology


  • IFNA8 protein, human
  • IL7 protein, human
  • Interferon-alpha
  • Interleukin-7
  • Interleukin-7 Receptor alpha Subunit
  • Ki-67 Antigen
  • STAT5 Transcription Factor