# Dual role of circulating and mucosal Vδ1 T cells in the control of and contribution to persistent HIV-1 infection

## TL;DR

This study reveals that Vδ1 T cells both help control and contribute to persistent HIV-1 infection in the body.

## Contribution

The study identifies a novel dual role of Vδ1 T cells in both inhibiting and contributing to HIV-1 persistence.

## Key findings

- Vδ1 T cells in the gastrointestinal mucosa inhibit HIV-1 replication while also harboring HIV-1 DNA.
- Circulating Vδ1 T cells contain replication-competent HIV-1 DNA.
- TCR activation of Vδ1 T cells increases CD4 expression, making them more susceptible to HIV-1 infection.

## Abstract

Curative strategies for human immunodeficiency virus (HIV-1) infection are hindered by incomplete characterization of the latent reservoir and limited enhancement of anti-HIV immune responses. In this study, we identified a novel dual role for peripheral and tissue-resident Vδ1 T cells within the gastrointestinal mucosa of virally suppressed people with HIV. Phenotypic analyses identified an increased frequency of highly differentiated, cytotoxic effector Vδ1 T cells that exerted potent inhibition of HIV-1 replication in vitro coinciding with direct increases in cytolytic function. Conversely, we detected an enrichment of HIV-1 DNA in tissue-resident CD4+Vδ1 T cells in situ. Despite low CD4 expression, we found circulating Vδ1 T cells also contained HIV-1 DNA which was replication-competent. We show that TCR-mediated activation of peripheral Vδ1 T cells induced de novo upregulation of CD4 providing a plausible mechanism for increased permissibility to infection. These findings highlight juxtaposing roles for Vδ1 T cells in HIV-1 persistence including significant contribution to tissue reservoirs.