Development of Vγ2Vδ2+ T cell responses during active mycobacterial coinfection of simian immunodeficiency virus-infected macaques requires control of viral infection and immune competence of CD4+ T cells

Vgamma2Vdelta2(+) T cells play a role in antimicrobial responses. It is unknown whether adaptive Vgamma2Vdelta2(+) T cell responses during active mycobacterial coinfection of human immunodeficiency virus-infected humans can be generated during effective antiretroviral treatment. Here, simian immunodeficiency virus (SIV)mac-infected macaques previously exposed to bacille Calmette-Guerin (BCG) were reinfected with BCG, were treated either with tenofovir or tenofovir plus indinavir, and were assessed for the development of Vgamma2Vdelta2(+) T cell responses during active BCG coinfection. A restored capacity of Vgamma2Vdelta2(+) T cells to undergo major expansions and pulmonary migration during active BCG coinfection was detected after simultaneous BCG reinfection and treatment with tenofovir of the SIVmac-infected macaques. Interestingly, a restored expansion of Vgamma2Vdelta2(+) T cells in the SIVmac/BCG-coinfected macaques was detectable, even though antiretroviral treatment was initiated 1 month after BCG reinfection. Importantly, the restored expansion of Vgamma2Vdelta2(+) T cells coincided with increases in numbers of purified protein derivative-specific interferon-gamma-producing CD4(+) T cells and increases in the magnitude of their proliferative responses. In contrast, the SIVmac-infected control macaques exhibited diminished responses of Vgamma2Vdelta2(+) T cells and mycobacterium-specific CD4(+) T cells during active BCG coinfection. Our results suggest that the development of adaptive immune responses of phosphoantigen-specific Vgamma2Vdelta2(+) T cells during active mycobacterium/HIV coinfection requires control of viral infection and immune competence of peptide-specific CD4(+) T cells.