Cytotoxic CX3CR1+ Vδ1 T cells clonally expand in an interplay of CMV, microbiota, and HIV-1 persistence in people on antiretroviral therapy

We performed a comprehensive characterization of Vδ1 T cells in blood of people with HIV-1 on antiretroviral therapy and HIV-seronegative controls, in a substudy of the ANRS EP61 GALT study (NCT02906137). We deciphered the single-cell transcriptome of Vδ1 cells. Vδ1 T cells were mainly terminally differentiated effectors that 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. 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.