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

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Abstract
Vγ2Vδ2+ T cells play a role in antimicrobial responses. It is unknown whether adaptive Vγ2Vδ2+ 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-Guérin (BCG) were reinfected with BCG, were treated either with tenofovir or tenofovir plus indinavir, and were assessed for the development of Vγ2Vδ2+ T cell responses during active BCG coinfection. A restored capacity of Vγ2Vδ2+ 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 Vγ2Vδ2+ 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 Vγ2Vδ2+ T cells coincided with increases in numbers of purified protein derivative-specific interferon-γ-producing CD4+ T cells and increases in the magnitude of their proliferative responses. In contrast, the SIVmac-infected control macaques exhibited diminished responses of Vγ2Vδ2+ 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 Vγ2Vδ2+ T cells during active mycobacterium/HIV coinfection requires control of viral infection and immune competence of peptide-specific CD4+ T cells.