title: 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.
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.
authors: School of Pathology and Laboratory Medicine, University of Western Australia, Crawley, Western Australia 6009, Australia; and.
authors: Lilian
authors: L
authors: Cha
authors: School of Pathology and Laboratory Medicine, University of Western Australia, Crawley, Western Australia 6009, Australia; and.
authors: Emma
authors: E
authors: de Jong
authors: School of Pathology and Laboratory Medicine, University of Western Australia, Crawley, Western Australia 6009, Australia; and Department of Clinical Immunology, Royal Perth Hospital and PathWest Laboratory Medicine, Perth, Western Australia 6000, Australia.
authors: Martyn A
authors: MA
authors: French
authors: School of Pathology and Laboratory Medicine, University of Western Australia, Crawley, Western Australia 6009, Australia; and sonia.fernandez@uwa.edu.au.
authors: Sonia
authors: S
authors: Fernandez
mesh_terms: D000328:Adult; D000368:Aged; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects*; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D005260:Female; D015658:HIV Infections / Q000276:immunology* / Q000473:pathology; D006801:Humans; D016898:Interferon-alpha / Q000276:immunology / Q000494:pharmacology*; D015851:Interleukin-7 / Q000276:immunology*; D053699:Interleukin-7 Receptor alpha Subunit / Q000276:immunology; D019394:Ki-67 Antigen / Q000276:immunology; D008297:Male; D008875:Middle Aged; D050799:STAT5 Transcription Factor / Q000276:immunology
chemical_list: C554164:IFNA8 protein, human; C508605:IL7 protein, human; D016898:Interferon-alpha; D015851:Interleukin-7; D053699:Interleukin-7 Receptor alpha Subunit; D019394:Ki-67 Antigen; D050799:STAT5 Transcription Factor