HIV-2-SPECIFIC CYTOTOXIC T-LYMPHOCYTE ACTIVITY IS INVERSELY RELATED TO PROVIRAL LOAD

Objectives: To characterize HIV-specific cytotoxic T-lymphocyte (CTL) activities in HIV-2-infected individuals and to relate these to HIV-2 proviral load. Methods: Peripheral blood mononuclear cells were collec ted from 16 HIV-2-seropositive and four HIV-1/-2 dually seropositive s ubjects. CTL were restimulated with autologous phytohaemagglutinin-sti mulated blasts and CTL activities in 'bulk' cultures were evaluated 7 and 14 days later by a standard Cr-51-release assay using autologous B -cell lines infected with recombinant vaccinia expressing HIV-2 Gag, P ol or Nef protein. Proviral load was quantified by polymerase chain re action (PCR) which used HIV-2 long terminal repeat primers and an exte rnal standard control made by an HIV-2(CBL-22) chronically infected C8 166 cell line. A biotinylated primer was used to capture the S-35 dATP -incorporated secondary PCR product in a quantitative radiometric assa y. Results: After 14 days of culture CTL responses against Gag or Pol protein were seen in 18 (90.0%) and 14 (70.0%) out of 20 subjects, res pectively, whereas a CTL response was noted against Nef protein in fiv e (25.0%) out of 20 subjects. In 14 (70.0%) out of 20 subjects multipl e HIV proteins were simultaneously recognized. The sum of specific lys is (%) against HIV-2 Gag, Pol and Nef at 30:1 effector-to-target ratio , or specific lysis of the dominant CTL response, correlated strongly with HIV-2 proviral load expressed as copies per 10(5) CD4+ cells (r=- 0.625, P=0.003 and r=-0.674, P=0.001, respectively). Conclusion: HIV-2 -specific CTL to multiple gene products was demonstrated in most HIV-2 -infected individuals. An inverse correlation between the level of CTL activity and proviral load was found, which supports the hypothesis t hat CTL are important in the control of HIV-2 replication.