Journal of Leukocyte Biology
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Originally published online as doi:10.1189/jlb.1207847 on May 21, 2008

Published online before print May 21, 2008
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(Journal of Leukocyte Biology. 2008;84:371-379.)
© 2008 by Society for Leukocyte Biology

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

Jean-Saville Cummings*,{dagger}, Cristiana Cairo*, Cheryl Armstrong*, Charles E. Davis* and C. David Pauza*,1

* Institute of Human Virology, University of Maryland School of Medicine, and
{dagger} Graduate Program in Life Sciences, University of Maryland, Baltimore, Maryland, USA

1 Correspondence: Institute of Human Virology, University of Maryland School of Medicine, 725 W. Lombard St., N546, Baltimore, MD 21201, USA. E-mail: cdpauza{at}ihv.umaryland.edu

ABSTRACT

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/mm3. 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.

Key Words: natural immunity • gamma delta • effector memory • cytotoxicity






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