title: CD8+ T cells from most HIV-1-infected patients, even when challenged with mature dendritic cells, lack functional recall memory to HIV gag but not other viruses.
abstract: Chronically HIV-1-infected patients fail to contain their viremia despite high frequencies of HIV-1-specific, IFN-gamma-producing CD8(+) T cells. However, these cells are known to exhibit both phenotypic and functional defects. We tested if mature dendritic cells (DC) could correct defective HIV-1 gag-specific T cell responses and if responses to other viral antigens were comparably affected. The circulating gag-specific CD8(+) T cells in fresh blood reliably produced IFN-gamma but lacked IL-2 and high perforin levels and failed to expand significantly during culture with mature DC presenting HIV-1 gag peptides. In contrast, CD8(+) T cells from long-term nonprogressors contained gag-specific IFN-gamma and IL-2 double producers, and the numbers of IFN-gamma producers expanded approximately 15-fold during culture with DC. DC from chronically infected patients could expand IFN-gamma- and IL-2-producing cells specific for influenza, cytomegalovirus and Epstein Barr virus, and the expansions were comparable to those in healthy donors. When the proliferative capacity of CD8(+) T cells from progressor patients was assessed by CFSE dilution, proliferation to other viral antigens was more vigorous than to HIV-1 gag. Therefore, monocyte-derived DC from HIV patients present viral antigens effectively, but there is a selective inability to expand CD8(+) IFN-gamma-producing and IFN-gamma and IL-2 double-producing T cells when challenged with HIV-1 gag.
authors.affiliation: Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, NY 10021, USA.
authors.forename: Geraldine
authors.initials: G
authors.lastname: Arrode
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Finke
authors.forename: Henry
authors.initials: H
authors.lastname: Zebroski
authors.forename: Frederick P
authors.initials: FP
authors.lastname: Siegal
authors.forename: Ralph M
authors.initials: RM
authors.lastname: Steinman
mesh_terms: D017951:Antigen Presentation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016022:Case-Control Studies; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000276:immunology / Q000473:pathology; D015683:Gene Products, gag / Q000276:immunology*; D015488:HIV Antigens; D015658:HIV Infections / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D018023:HIV Seronegativity / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins
chemical_list: D015683:Gene Products, gag; D015488:HIV Antigens; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin; D007371:Interferon-gamma