ObjectivesCorrelation of lysis of autologous CD4+ target cells by cytotoxic lymphocytes from HIV-seropositive patients to target activation, viral replication, and major histocompatibility complex (MHC) restriction.DesignTwenty-two HIV-infected patients were evaluated for lysis of activated CD4+ cells, concurrent with measurement of proliferation of the target cells, and with viral replication.MethodsTitrated standard51Cr-release assays for specific effector-to-target cell recognition, blocking antibodies and cell depletion for cell characterization, incorporation of [3H]- thymidine for proliferation, and p24 antigen capture assays for viral replication.ResultsHIV-infected patients had cytotoxic lymphocytes capable of recognizing activated CD4+ target cells in a non-MHC-restricted manner. The lysis depended on the degree of target activation, and was independent of viral replication.ConclusionsThis cytolytic activity is unique to HIV-infected patients, and is suggestive of activation-induced cell death that may contribute to the progressive depletion of CD4+ lymphocytes during HIV pathogenesis.