Impacts of HIV infection on Vgamma2Vdelta2 T cell phenotype and function: a mechanism for reduced tumor immunity in AIDS.
HIV infection causes rapid and lasting defects in the population of Vgamma2Vdelta2 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- Vgamma2Vdelta2 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. Vgamma2 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 Vgamma2 cells from HIV+ PBMC that may be a mechanism for depletion of Vgamma2 cells during disease. In addition to the well-characterized defects in the Vgamma2 repertoire and functional responses to phosphoantigen, the proportion of CD27-/CD45RA- Vgamma2Vdelta2 T cells after isopentenyl pyrophosphate stimulation was reduced sharply in HIV+ donors versus controls. Thus, HIV infection has multiple impacts on the circulating Vgamma2Vdelta2 T cell population that combine to reduce the potential effector activity in terms of tumor cytotoxicity. Changes in Vgamma2Vdelta2 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.
Cummings
Jean-Saville
JS
Institute of Human Virology, University of Maryland School of Medicine, 725 W. Lombard St., N546, Baltimore, MD 21201, USA.
Cairo
Cristiana
C
Armstrong
Cheryl
C
Davis
Charles E
CE
Pauza
C David
CD
D000163:Acquired Immunodeficiency Syndrome / Q000150:complications / Q000276:immunology*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000276:immunology; D017493:Leukocyte Common Antigens / Q000172:deficiency; D008223:Lymphoma / Q000235:genetics / Q000276:immunology; D009369:Neoplasms / Q000453:epidemiology / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000172:deficiency; D019014:fas Receptor / Q000235:genetics
D016692:Receptors, Antigen, T-Cell, gamma-delta; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D019014:fas Receptor; D017493:Leukocyte Common Antigens