017 Single-cell T cell receptor (TCR) repertoire of skin and blood reveals skin-specific characteristics in health and HIV infection

Human skin harbours a large proportion of the resident memory T (Trm) cells of the body. Trm cells promote immune homeostasis and exert anti-microbial and anti-cancer function in tissue. We recently demonstrated that skin Trm cells are permanently depleted in people living with HIV (PLWH) with a low nadir and possibly replaced by blood-derived T cells. We linked the loss of Trm cells in PLWH with the increased risk of developing cutaneous and mucosal cancer. The T-cell receptor (TCR) diversity analysis with next generation sequencing might give new insights into the biology of skin Trm cells at homeostasis and in HIV. We investigated the TCR profile of skin- compared to blood-derived T cells in healthy controls (HC) and PLWH (n=5). We first performed bulk RNA-sequencing to study diversity, richness and clonality distribution among the study groups. We then continued with single-cell RNA-Sequencing (scRNA-Seq) coupled with single-cell TCR-Sequencing (scTCR-Seq) to get more insights into the distribution of TCR clones in the different skin and T cell clusters. We observed that only few clones are shared between skin and blood in healthy controls (8.39%), suggesting that Trm cells are quite self-sustained with scarce immune interactions with other compartments. On the contrary, the percentage of TCR clones shared between skin and blood circulating T cells in PLWH was 24.5% and mostly represented by effector memory CD8+ T cells. Further analysis suggested an oligoclonal expansion of the TCR repertoire in CD8+ T cells of PLWH. Considering the increased risk in PLWH for psoriasis and cancer, we believe that the ongoing analysis will bring new insights into the pathogenesis of inflammatory skin diseases and cancer susceptibility of barrier organs.