LONGITUDINAL-STUDY OF HIV-SPECIFIC CYTOTOXIC LYMPHOCYTES IN HIV TYPE 1-INFECTED PATIENTS - RELATIVE BALANCE BETWEEN HOST IMMUNE-RESPONSE AND THE SPREAD OF HIV TYPE-1 INFECTION

To evaluate the contribution of a specific cytotoxic response in the c ontrol of HIV infection in relation to clinical status, we performed s erial analysis of anti-Env and anti-Gag cytotoxic activity in 13 infec ted individuals over a 6- to 10-year period, using cryopreserved perip heral blood mononuclear cells (PBMCs), Autologous EBV-transformed B ce ll lines infected in vitro with recombinant vaccinia viruses expressin g HIV-1 env and gag genes were used as targets, Without any stimulatio n of the effector cells, we were able to show an anti-HIV cytotoxic ac tivity in the PBMCs of 12 of 13 HIV-1-infected patients, consistent wi th chronic immune activation in HIV infection, Different patterns of H IV-specific cytotoxic activity were observed, and the extent of this c ytotoxic response varied between the clinically defined groups of indi viduals, No direct relationship was observed with the number of CD4 an d CDS lymphocytes during the observation period, However, patients who remained asymptomatic had a more vigorous cytotoxic response than pat ients with clinical deterioration during the observation period, and a significant difference was observed for HIV Gag-specific CTL activity , From these data, we suggest that the HIV-specific cytotoxic response has a protective role in the course of HIV infection.