CD8⁺ T-cells from HIV-infected patients can either augment or abrogate HIV-specific lymphoproliferation

Despite the presence of activated CD8⁺ T-cells that have been identified in infected individuals, these cells do not overcome natural HIV infection. To understand this better, we analyzed the CD8⁺ cell-dependent HIV-specific lymphoproliferation that occurs after HIV infection. Our study group of 36 individuals included 11 asymptomatic and 16 symptomatic patients (12 ARC and 4 AIDS), as well as HIV-seronegative controls. After CD8⁺ cell depletion of PBMC cultures, the remaining cells were tested for proliferation during culture with a well-defined and immunodominant gp41-derived HIV analog, gp41{8}. After CD8⁺ cell depletion, three functional outcomes, which differed in accordance with the disease status of the individual, were consistently recorded, namely (i) an "abrogation effect," (ii) an "augmentation effect," or (iii) "no effect." First, removal of CD8⁺ cells from PBMC cultures abrogated gp41{8}-specific lymphoproliferation in gp41{8}-specific responders. Paradoxically, in other patients, including 5 symptomatics, the same inhibition of CD8⁺ cell function caused significant augmentation of gp41{8}-specific lymphoproliferation. These results suggest that the subpopulations of CD8⁺ T-cells that predominate at different stages of HIV-induced disease have different functional properties, including the ability to modulate HIV-specific cell-mediated immunity.