Impacts of HIV infection on Vγ2Vδ2 T cell phenotype and function: a mechanism for reduced tumor immunity in AIDS

Abstract

HIV infection causes rapid and lasting defects in the population of Vγ2Vδ2 T cells. To fully describe the impact of HIV, we examined PBMC samples from HIV+ patients receiving highly active antiretroviral therapy, who had displayed prolonged viral control and CD4 counts above 300 cells/mm³. We observed lower frequencies of CD27–/CD45RA– Vγ2Vδ2 cells in HIV+ individuals when compared with controls, coupled with an increased proportion of CD45RA+ cells. These changes were common among 24 HIV+ patients and were not related to CD4 cell count or viral RNA burden. Vγ2 cells from HIV+ individuals had lower expression of Granzyme B and displayed reduced cytotoxicity against Daudi targets after in vitro stimulation. There was increased expression of FasR (CD95) on Vγ2 cells from HIV+ PBMC that may be a mechanism for depletion of Vγ2 cells during disease. In addition to the well‐characterized defects in the Vγ2 repertoire and functional responses to phosphoantigen, the proportion of CD27–/CD45RA– Vγ2Vδ2 T cells after isopentenyl pyrophosphate stimulation was reduced sharply in HIV+ donors versus controls. Thus, HIV infection has multiple impacts on the circulating Vγ2Vδ2 T cell population that combine to reduce the potential effector activity in terms of tumor cytotoxicity. Changes in Vγ2Vδ2 T cells, along with concomitant effects on NK and NKT cells that also contribute to tumor surveillance, may be important factors for elevating the risk of malignancy during AIDS.