The Potential Role of CD16+ Vγ2Vδ2 T Cell-Mediated Antibody-Dependent Cell-Mediated Cytotoxicity in Control of HIV Type 1 Disease

Increasing evidence has suggested that HIV infection severely damages the V2V2 (V2) T cells that play an important role in the first-line host response to infectious disease. However, little is known about V2 T cell-mediated antibody-dependent cell-mediated cytotoxicity (ADCC) in HIV disease. We found that although the CD16(+) V2 T cell subset hardly participated in phosphoantigen responses dominated by the CD16(-) V2 T cell subset, the potency of the ADCC function of V2 T cells was correlated with the frequency of the CD16(+) subset. Thus, two distinct and complementary V2 T cell subsets discriminated by CD16 were characterized to explore the respective impacts of HIV-1 infection on them. HIV-1 disease progression was not only associated with the phosphoantigen responsiveness of the CD16(-) V2 subset, but also with the ability of the CD16(+) V2 subset to kill antibody-coated target cells. Furthermore, both of the two V2 functional subsets could be partially restored in HIV-infected patients with antiretroviral therapy. Notably, in the context of an overall HIV-mediated V2 T cell depletion, despite the decline of phosphoantigen-responsive CD16(-) V2 cells, CD16(+) V2 cell-mediated ADCC was not compromised but exhibited a functional switch with dramatic promotion of degranulation in the early phase of HIV infection and chronic infection with slower disease progression. Our study reveals functional characterizations of the two V2 T cell subsets with different activation pathways during HIV-1 infection and provides a rational direction for activating the CD16(+) V2 T cells capable of mediating ADCC as a means to control HIV-1 disease.