HIV-mediated gammadelta T cell depletion is specific for Vgamma2+ cells expressing the Jgamma1.2 segment.

Circulating Vgamma2/Vdelta2(+) T cells, normally constituting 3-6% of all CD3(+) T cells in blood, are severely depleted after HIV infection. The mechanism(s) for Vgamma2/Vdelta2(+) T cell depletion are unknown, partly because these cells are CD4(-) and resistant to HIV infection. To determine whether this cell depletion was general for all Vgamma2(+) cells or specific for an individual subset, we analyzed the Vgamma2 repertoire and found consistent differences between HIV(+) and uninfected control samples. The change in Vgamma2 repertoire was the result of preferentially depleting only those Vgamma2 cells that express the Jgamma1.2 segment. The specific loss of Vgamma2-Jgamma1.2(+) cells was polyclonal, as the Vgamma subset retained normal diversity even after HIV infection, and loss occurred without significant changes in the paired chain (Vdelta2) repertoire, or in the alternate Vdelta1 chain repertoire. Specific depletion of Vgamma2-Jgamma1.2/Vdelta2 T cells is the first evidence of a common, T cell receptor-dependent cell loss in HIV disease and it provides a clear example of bystander cell depletion. Vgamma2-Jgamma1.2/Vdelta2 T cells mediate potent responses to microbial pathogens including HIV, and loss of this subset is an important aspect of AIDS pathogenesis.