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Impacts of HIV infection on Vγ2Vδ2 T cell phenotype and function: a mechanism for reduced tumor immunity in AIDS
Author(s) -
Cummings JeanSaville,
Cairo Cristiana,
Armstrong Cheryl,
Davis Charles E.,
Pauza C. David
Publication year - 2008
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.1207847
Subject(s) - biology , immunology , granzyme , population , granzyme b , cytotoxic t cell , immune system , peripheral blood mononuclear cell , immunity , cellular immunity , t cell , cd8 , in vitro , perforin , medicine , biochemistry , environmental health
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/mm 3 . 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.