| Description: |
Vδ 1 γδ T cells are key players in innate and adaptive immunity, particularly at mucosal interfaces such as the gut. An increase in circulating Vδ 1 cells has long been observed in people with HIV-1, but remains poorly understood. We performed a comprehensive characterization of Vδ 1 T cells in blood and duodenal intra-epithelial lymphocytes, obtained from endoscopic mucosal biopsies of 15 people with HIV-1 on antiretroviral therapy and 15 HIV-seronegative controls, in a substudy of the ANRS EP61 GALT study (NCT02906137). We deciphered the phenotype, functional profile, single-cell transcriptome and repertoire of Vδ 1 cells and unraveled their relationships with the possible triggers involved, in particular CMV and microbiota. We also assessed whether Vδ 1 T cells may play a role in controlling the HIV-1 reservoir. Vδ 1 T cells were mainly terminally differentiated effectors that clonally expanded in the blood with some trafficking with the gut of people with HIV-1. Most expressed CX3CR1 and displayed a highly cytotoxic profile, but low cytokine production, supported by a transcriptomic shift towards enhanced effector lymphocytes. This expansion was associated with CMV status and markers of occult replication, but also with changes in the duodenal and blood-translocated microbiota. Cytotoxic, but not IFN-γ-producing, Vδ 1 T cells were negatively associated with cell-associated HIV-1 RNA in both the blood and duodenal compartments. The increase in Vδ1 T cells observed in people with HIV-1 has multiple triggers, particularly CMV and microbiota, and may in turn contribute to the control of the HIV-1 reservoir. |