title: Immunosenescent CD57+CD4+ T-cells accumulate and contribute to interferon-γ responses in HIV patients responding stably to ART.
abstract: HIV-infected individuals responding to antiretroviral therapy (ART) after severe CD4+ T-cell depletion may retain low responses to recall antigens [eg: cytomegalovirus (CMV)] and altered expression of T-cell co-stimulatory molecules consistent with immunosenescence. We investigated the capacity of phenotypically senescent cells to generate cytokines in HIV patients receiving long-term ART (n = 18) and in healthy controls (n = 10). Memory T-cells were assessed by interferon (IFN)-γ ELISpot assay and flow cytometrically via IFN-γ or IL-2. Proportions of CD57(bright)CD28(null) CD4+ T-cells correlated with IFN-γ responses to CMV (p =0.009) and anti-CD3 (p =0.002) in HIV patients only. Proportions of CD57(bright)CD28(null) CD8+T-cells and CD8+ T-cell IFN-γ responses to CMV peptides correlated in controls but not HIV patients. IL-2 was predominantly produced by CD28+T-cells from all donors, whereas IFN-γ was mostly produced by CD57+ T-cells. The findings provide evidence of an accumulation of immunosenescent T-cells able to make IFN-γ. This may influence the pathogenesis of secondary viral infections in HIV patients receiving ART.
authors.affiliation: School of Pathology and Laboratory Medicine, University of Western Australia and PathWest Laboratory Medicine, Perth, Australia. sonia.fernandez@uwa.edu.au
authors.forename: Sonia
authors.initials: S
authors.lastname: Fernandez
authors.forename: Martyn A
authors.initials: MA
authors.lastname: French
authors.forename: Patricia
authors.initials: P
authors.lastname: Price
mesh_terms: D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D001315:Australia; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018959:CD57 Antigens / Q000096:biosynthesis* / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D016022:Case-Control Studies; D049109:Cell Proliferation; D016922:Cellular Senescence / Q000276:immunology*; D060085:Coinfection; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000821:virology; D005260:Female; D006678:HIV / Q000276:immunology*; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000821:virology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D007376:Interleukin-2 / Q000096:biosynthesis / Q000276:immunology; D008297:Male; D008875:Middle Aged
chemical_list: D019380:Anti-HIV Agents; D018959:CD57 Antigens; D007376:Interleukin-2; D007371:Interferon-gamma