Role of CD8(+) cell-produced anti-viral factors in protective immunity in HIV-2-exposed but seronegative macaques resistant to intrarectal SIVsm challenge

The cell-mediated immune response is likely to be important in controlling HIV/SIV infection. There is evidence that beta -chemokines and other, as ye t unknown, anti-viral factors play a role in host defence against HIV infec tion. We reported previously that HIV-2 exposed but seronegative cynomolgus macaques developed SIV-specific cytotoxic T lymphocytes and were resistant to mucosal SIV challenge. The aim of this study was to examine CD8(+) cell -dependent production of beta -chemokines and other anti-viral factors in t hese macaques. The animals, selected from among 17 monkeys enrolled in two separate experiments, were either treated with an anti-viral drug or immuni zed passively with HIV-2 antibody-positive serum. Three of these monkeys we re protected against repeated HIV-2 challenge and were also able to control SIV infection 3 years later. Control samples were obtained from four macaq ues that became SIV infected and from 39 naive animals. The three resistant monkeys showed significantly higher production of RANTES and MIP-1 alpha t han the 39 naive animals. In addition, SIV infection was suppressed by CD8( +) cell culture supernatants of these monkeys. However, antibodies to chemo kines only partially neutralized CD8(+) cell-mediated SIV suppression indic ating that the anti-viral activity observed in these monkeys was the result of combined action of several inhibitory factors.