HIV-Mediated γδ T Cell Depletion Is Specific for V γ 2 + Cells Expressing the J γ 1.2 Segment

Circulating Vγ2/Vδ2⁺ T cells, normally constituting 3-6% of all CD3⁺ T cells in blood, are severely depleted after HIV infection. The mechanism(s) for Vγ2/Vδ2⁺ 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 Vγ2⁺ cells or specific for an individual subset, we analyzed the Vγ2 repertoire and found consistent differences between HIV⁺ and uninfected control samples. The change in Vγ2 repertoire was the result of preferentially depleting only those Vγ2 cells that express the Jγ1.2 segment. The specific loss of Vγ2-Jγ1.2⁺ cells was polyclonal, as the Vγ subset retained normal diversity even after HIV infection, and loss occurred without significant changes in the paired chain (Vδ2) repertoire, or in the alternate Vδ1 chain repertoire. Specific depletion of Vγ2-Jγ1.2/Vδ2 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. Vγ2-Jγ1.2/Vδ2 T cells mediate potent responses to microbial pathogens including HIV, and loss of this subset is an important aspect of AIDS pathogenesis.