Interleukin-7 enhances memory CD8(+) T-cell recall responses in health but its activity is impaired in human immunodeficiency virus infection.
Memory CD8(+) T cells regain function during a recall response, but the requirement of signals in addition to antigen during a secondary immune response is unknown. In this study, the ability of interleukin-7 (IL-7) to enhance memory CD8(+ ) CD45RA(- ) CD127(+) T-cell responses in health and in human immunodeficiency virus (HIV) infection was investigated. CD8(+) T-cell-depleted peripheral blood mononuclear cells (PBMCs) from HIV(-) and untreated HIV(+) donors were pulsed with a cytomegalovirus/Epstein-Barr virus/influenza (CEF) peptide pool, and co-cultured with autologous memory CD8(+) T cells in the presence of IL-7. Cell survival and the function of memory CD8(+) T-cell subsets were then evaluated. Memory CD8(+) T-cell proliferation and interferon-γ (IFN-γ) production was enhanced by the presence of antigen, and the addition of IL-7 further enhanced antigen-induced proliferation. In HIV(+) individuals, the presence of antigen enhanced IFN-γ production to a small degree but did not enhance proliferation. Lastly, IL-7 did not enhance antigen-mediated proliferation of memory CD8(+) T cells from HIV(+) individuals. IL-7 therefore appears to have a role in secondary immune responses and its activity is impaired in memory CD8(+) T cells from HIV(+) individuals. These results further our understanding of the signals involved in secondary immune responses, and provide new insight into the loss of CD8(+) T-cell function in HIV infection.
O'Connor
Alison M
AM
Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Canada.
Crawley
Angela M
AM
Angel
Jonathan B
JB
D000956:Antigens, Viral / Q000276:immunology / Q000494:pharmacology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D018920:Coculture Techniques; D006678:HIV / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007156:Immunologic Memory / Q000187:drug effects / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology; D015851:Interleukin-7 / Q000276:immunology*; D010455:Peptides / Q000276:immunology / Q000494:pharmacology; D014764:Viral Proteins / Q000276:immunology / Q000494:pharmacology
D000956:Antigens, Viral; C508605:IL7 protein, human; D015851:Interleukin-7; D010455:Peptides; D014764:Viral Proteins; D007371:Interferon-gamma