Characterization of simian immunodeficiency virus-specific T-cell-mediated cytotoxic response of infected rhesus macaques

Four juvenile rhesus macaques were infected with simian immunodeficiency virus (SIV)(MAC). Freshly isolated peripheral blood mononuclear cells (PBMC) from these SIV(MAC)-infected and from uninfected control macaques were assessed for cytotoxic T-lymphocyte (CTL) activity monthly for 7 consecutive months, beginning 2 months after infection. Target cells consisted of major histocompatibility complex (MHC) haploidentical parental PBMC which were stimulated with mitogen and then pulsed with heat-killed SIV(MAC). CTL activity was demonstrated on all four infected animals. The effector cells are T cells which mediate cytotoxicity against SIV(MAC)-pulsed target cells in an MHC-restricted manner. Furthermore, the cytotoxicity is virus specific and predominantly, if not exclusively, mediated by CD8+ T cells; it is also MHC class-I restricted. Incubation of target cells with leupeptin prior to the cytotoxic assay inhibited target cell generation, suggesting that viral antigens are processed via an endocytic pathway.