Detection of simian immunodeficiency virus (SIV)-specific T-cell-mediated cytotoxicity in the peripheral blood from infected cynomolgus monkeys

We have previously demonstrated that peptide immunization restimulates the memory CD4 T-cell response, but fails to induce cytotoxic T lymphocyte (CTL ) in cynomolgus macaques. To examine the nature of protective immunity to s imian immunodeficiency virus (SIV) in this study. freshly isolated peripher al blood mononuclear cells (PBMC) from four infected juvenile cynomolgus ma caques and from three uninfected control macaques were assessed for CTL act ivity monthly for 9 consecutive months, beginning 1 month after detection o f infection. Target cells consisted of major histocompatibility (MHC) haplo identical parental PBMC which were stimulated with mitogen and then pulsed with heat-killed SIVcyn. CTL activity was demonstrated in PBMCs from all fo ur infected animals. The effector cells are T cells which mediate cytotoxic ity against SIVcyn-pulsed target cells in an MHC-restricted manner. Further more, the cytotoxicity is virus specific and predominantly, if not exclusiv ely, mediated by CD8(+) T cells; it is also MHC class I restricted. incubat ion of target cells with pepstalin A during antigen pulsing prior to the cy totoxic assay inhibited target cell generation, suggesting that viral antig ens are processed via an endocytic pathway.