Anti-HIV-1 effector potential of mucosal-associated invariant T (MAIT) cells — ASN Events

Anti-HIV-1 effector potential of mucosal-associated invariant T (MAIT) cells (#85)

Adam M Spivak 1 , Michael S Bennett 1 , McKenna L Coletti 1 , Shubhanshi Trivedi 1 , Fabio AP Barrios 1 , Matthew T Rondina 2 , Daniel T Leung 1
  1. Division of Infectious Diseases, University of Utah School of Medicine, Salt Lake City, UT, United States
  2. Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA

In persons living with HIV infection, antiretroviral therapy (ART) is not curative due to the persistence of replication-competent proviruses primarily in long-lived memory CD4+ T cells. One strategy to eradicate this latent reservoir, termed ‘shock and kill,’ involves administration of compounds able to reverse proviral latency in order for the immune system to target these cells. In a recent clinical trial of panobinostat, the frequency and activity of NK cells and plasmacytoid dendritic cells, but not HIV-1-specific CD8+ T cells, were associated with decreased HIV-1 proviral DNA. This in vivo data identifies the cytotoxic antiviral response of innate lymphocytes as a highly promising means to target the latent reservoir. Recent reports have identified that MAIT cells are able to target virally infected cells. Thus, we hypothesize that MAIT cells are uniquely-armed to aid in the clearance of the HIV-1 reservoir in the setting of latency reversal. To investigate this, we isolated peripheral blood mononuclear cells (PBMCs) from HIV-1-infected individuals and stimulated with microbial antigen. Using single-cell paired clonality-functionality sequencing, we show that antigen-stimulated MAIT cells have a unique clonal distribution in HIV-1-infected individuals who control viremia and maintain normal T cell counts without ART (known as elite controllers), distinct from both aviremic patients on ART and uninfected individuals. We also observed that MAIT clones expanded from PBMCs, when activated in both TCR-dependent and TCR-independent manners, exhibit potent cytotoxic activity against HIV-1-infected infected cells in vitro.  In conclusion, MAIT cells represent a previously unexplored effector cell population that has the potential to contribute to recognition and clearance of HIV-1-infected cells in the context of latency reversal.