The Role of CD8+ T-cell Response in HIV Infection

CD8+ T-cells with cytotoxic (CTL) activity play a pivotal role in controlling viral infections. Althoughmost patients chronically infected with HIV have CTL response against the virus, for reasons thatare not well understood this response is not able to successfully control viral replication. The crucialrole of this type of response has been clearly demonstrated in the setting of acute infection usingthe simian model of AIDS, in which a strong CTL response develops, supporting its role in humans.This approach has been possible due to the development of new assays to quantify CTL activity withgreat sensitivity and specificity. The interaction of CTL response and HIV during this acute stage ofinfection is crucial, since it most probably determines the viral set-point and thus the rate of HIVdisease progression.In the setting of chronic HIV infection, the use of tetrameric complexes and IFN-γ production assayshave made it possible to investigate the different functional aspects of these cells and have alsofacilitated the evaluation of this response in large patient populations. Defects in cytokine productionand in perforin expression have been found, as well as alterations in phenotypic maturation and alow proliferation of these cells. All these findings have been cited to explain the inability of CTLs toefficiently control virus replication. Nonetheless, accumulating evidence points toward an importantrole for CTL response in the partial containment of HIV replication in chronic infection. An especiallystrong support for this observation derives from studies analyzing the selective pressure exertedby the immune response over viral evolution. Very recently, longitudinal and cross-sectionalstudies in large populations of patients have demonstrated that viral evolution is in part driven byHIV-specific T-cell responses.