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

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 circulting 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.