Th180 - Single-cell Transcriptomes Reveal Unique CD8 T Cell Atlas Induced by Cytomegalovirus Viremia in Kidney Transplant Recipients

Harry Pickering – University of California, Los Angeles; Rajesh Parmar – University of California Los Angeles; Elaine Reed – University of California, Los Angeles

Abstract Text: Cytomegalovirus (CMV) infection is a risk factor for graft loss and mortality in solid-organ transplant and impacts the phenotype and function of T cells in kidney transplant recipients (KTRs). We performed single-cell RNA-sequencing of blood CD8 T cells from CMV seropositive (S/P) and seronegative (S/N) KTRs at Baseline (BL, 3-mo post-Tx), 1wk post-CMV viremia (1W), and long-term (LT, 1yr post-Tx), and propensity matched PCR- control groups to assess the temporal dynamics of CD8 T cells before and after PCR detection of CMV in KTRs experiencing CMV primary infection (S/N PCR+) and reactivation (S/P PCR+). CD8 T cells were markedly impacted by CMV serostatus and viremic episodes: late-differentiated cells were enriched in S/P patients at BL and LT, and at 1W S/N PCR+ KTRs were separated from S/P PCR+ KTRs. Pseudotime trajectory analysis of CMV viremia revealed cells from S/N PCR+ KTRs showed limited transcriptomic variation over-time with continuous enrichment in naïve and T stem cell memory phenotypes. Meanwhile, S/P PCR+ patients have greater longitudinal transcriptomic changes consisting of early (1W) expansion of terminally differentiated, senescent-like CD8 T cells with restricted capacity for cell proliferation, cell cycle progression, protein translation but high cytotoxicity, related functions needed for acute viremic control. Primary infection also resulted in poor CMV recall response post-Tx compared to reactivation. Our results suggest that CMV memory response can be difficult to establish and maintain after primary infection under immunosuppression, and strategies such as CMV vaccine could be helpful to induce pre-Tx CMV specific immunity and prevent CMV disease.