CD16 and CD57 Expressing Gamma Delta T Cells in Acute HIV-1 Infection are Associated with the Development of Neutralization Breadth

New HIV vaccine approaches are focused on eliciting broadly neutralizing antibodies. We characterized early gamma-delta (?d) T cell responses starting from pre-acquisition and during acute HIV infection (AHI) in participants previously characterized for neutralization breadth development. We found significant differences in ?d T cell surface marker expression in participants that developed neutralization breadth compared to those that did not. Activation of ?d T cells occurred within the first weeks of HIV acquisition and associated with viral load. Expression of CD16 on Vd1 T cells and CD57 on Vd2 T cells were found to be significantly higher in broad neutralizers during AHI, and associated with the development of neutralization breadth years later. In addition, the levels of CD16 on Vd1 T cells was associated with early production of founder virus Env-specific IgM. Thus, ?d T cells may promote development of neutralization breadth, which has implications for HIV vaccine strategies. Overall design: Gamma delta T cells were sorted from PBMCs from 22 participants at 4 time points: pre HIV acquisition, peak viral load (VL) (median days since first positive test for HIV-1 RNA = 18 days), set point VL (median days since first positive test for HIV-1 RNA = 42), and chronic HIV (median days since first positive test for HIV-1 RNA = 980). Sorted cells were then processed for bulk RNA sequencing.