Loss of T-cell cytotoxic responses in the course of HIV-1 infection

T-cell mediated cytotoxicity play an important role in the control of human immunodeficiency virus (HIV) infection. The polyclonal cytotoxic T lymphocyte (CTL) response against target cells infected with a recombinant vaccinia virus expressing Env, Gag, Nef or reverse transcriptase (RT) proteins has been studied in four groups of individuals: acquired immune deficiency syndrome (AIDS) patients, AIDS-related complex (ARC) patients, HIV-1 seropositive subjects and seronegative controls. CTL lines have been generated by non-specific stimulation with phytohemagglutinin and interleukin-2 and target cells have been prepared from autologous B lymphocytes. CTL from asymptomatic and ARC individuals recognized most of the various proteins of HIV-1 but those from AIDS patients had very low or absent responses to the majority of proteins, with the anti-Nef cytotoxic activity decreasing first. Two of 10 AIDS patients had demonstrable recognition of Gag p24, one of RT and eight patients had no recognition of any of the proteins. The effector cells were demonstrated to be predominantly of the CD8+ phenotype, using the appropriate monoclonal antibodies. When heterologous target cells were substituted for autologous cells, the cytotoxic response was abrogated in the vast majority of cases demonstrating its human leucocyte antigen (HLA) class I restriction. Among the 10 HIV-seronegative subjects, nine had no CTL activity against the various HIV-1 proteins but one subject was able to recognize Env and RT. In the evolution of HIV infection from the seropositive stage to AIDS, CTL polyclonal activities progressively decrease, with Nef responses disappearing first, then Env and Gag p55, followed by RT and Gag p24.