MHC-I NONRESTRICTED CYTOTOXIC ACTIVITY IN MACACA-SYLVANA EXPERIMENTALLY INOCULATED WITH HIV-2 AND SIV MAC

The anti-retrovirus cell-mediated immunity was repeatedly investigated in seven monkeys (Macaca sylvana). Four of these animals were injecte d with cell-free supernatants containing human immunodeficiency viruse s: two monkeys received HIV1 Bru (2.5 x 10(6) cpm), two received HIV2 Rod (1.5 x 10(6) cpm). Two additional animals were injected with a cel l-free supernatant containing simian immunodeficiency virus SIV/mac 25 1 (1.5 x 10(6) cpm) and the last animal served as control. The four ma caques infected with HIV2 Rod and SIV/mac 251 seroconverted. Freshly i solated and non stimulated peripheral blood mononuclear cells from the se infected macaques and from the uninfected control were repeatedly a ssessed for cytolytic activity. Target cells consisted of heterologous human cell lines expressing HIV1 Bru, HIV2 Rod or SIV/mac proteins. A significant cytotoxic activity, non-restricted at the major histocomp atibility complex class I (MHC-I), was demonstrated in one HIV2 Rod-in fected animal (F8) and in one SIV/mac 251-infected animal (M1). This l ast animal showed progressively diminishing cytolytic activity that wa s correlated with a pronounced decrease in CD4+ lymphocytes. An AIDS-l ike disease developed in MI, with presence of lymphadenopathy, weight loss, diarrhea and opportunistic infections. Cytotoxic activity was ac tive against SIV and HIV2-infected target cells in an MHC-unrestricted manner, it was specific to virus-infected cells and there was cross-r eactivity between HIV2 and SIV. Cytotoxic effectors appeared to be mai nly CD8+ cells. This model may prove to be very useful in evaluating t he capacity of candidate AIDS vaccines to elicit effective cell-mediat ed immune responses.