Impacts of HIV infection on V gamma 2V delta 2 T cell phenotype and function: a mechanism for reduced tumor immunity in AIDS

作者：Cummings Jean Saville; Cairo Cristiana; Armstrong Cheryl; Davis Charles E; Pauza C David^*

来源：Journal of Leukocyte Biology, 2008, 84(2): 371-379.

DOI：10.1189/jlb.1207847

• natural immunity
• gamma delta
• effector memory
• cytotoxicity

HIV infection causes rapid and lasting defects in the population of V gamma 2V delta 2 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/mm(3). We observed lower frequencies of CD27-/CD45RA- V gamma 2V delta 2 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. V gamma 2 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 V gamma 2 cells from HIV+ PBMC that may be a mechanism for depletion of V gamma 2 cells during disease. In addition to the well-characterized defects in the V gamma 2 repertoire and functional responses to phosphoantigen, the proportion of CD27-/CD45RA- V gamma 2V delta 2 T cells after isopentenyl pyrophosphate stimulation was reduced sharply in HIV+ donors versus controls. Thus, HIV infection has multiple impacts on the circulating V gamma 2V delta 2 T cell population that combine to reduce the potential effector activity in terms of tumor cytotoxicity. Changes in V gamma 2V delta 2 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.

• 出版日期2008-8-1