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

• Published in: European journal of immunology 2005-01, Vol.35 (1), p.159-170
• Main Authors: Arrode, Geraldine, Finke, Jennifer S., Zebroski, Henry, Siegal, Frederick P., Steinman, Ralph M.
• Format: Article
• Language: English
• Subjects: Antigen Presentation; Case-Control Studies; CD8+ T cell response; CD8-Positive T-Lymphocytes - immunology; Cell Differentiation; Cellular proliferation; Dendritic cells; Dendritic Cells - immunology; Dendritic Cells - pathology; Gene Products, gag - immunology; HIV Antigens; HIV Infections - etiology; HIV Infections - immunology; HIV Infections - pathology; HIV Seronegativity - immunology; HIV-1 - immunology; HIV‐1; Humans; Immunologic Memory; In Vitro Techniques; Interferon-gamma - biosynthesis; Interleukin-2 - biosynthesis; Lymphocyte Activation; Membrane Glycoproteins - biosynthesis; Perforin; Pore Forming Cytotoxic Proteins
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.200425744

Chronically HIV‐1‐infected patients fail to contain their viremia despite high frequencies of HIV‐1‐specific, IFN‐γ‐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‐γ 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‐γ and IL‐2 double producers, and the numbers of IFN‐γ producers expanded ∼15‐fold during culture with DC. DC from chronically infected patients could expand IFN‐γ‐ 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‐γ‐producing and IFN‐γ and IL‐2 double‐producing T cells when challenged with HIV‐1 gag.