Cytomegalovirus-associated CD57 + KLRG1 + CD8 + TEMRA T cells are associated with reduced risk of CMV viremia in kidney transplantation and chronic allograft dysfunction in lung transplantation

Cytomegalovirus (CMV) infection threatens outcomes across solid organ transplantation, but organ-specific differences in CMV immunity are incompletely understood. We investigated whether lung and kidney CMV infection drove similar immune profiles, hypothesizing that CMV-associated T cells would be associated with graft function. We longitudinally examined 41 lung transplant (LTx) recipients and 31 kidney transplant (KTx) recipients with CMV viremia, alongside non-viremic controls. We performed flow cytometry and single-cell protein and transcriptomic profiling (CITE-seq) on blood cells. Chronic lung allograft dysfunction (CLAD)-free survival and glomerular filtration rate decline-free survival were assessed by Cox proportional-hazards models. Terminal effector memory (TEMRA) CD8⁺ T cells segregated by expression of CD57 and KLRG1. CMV viremia led to expansion of CD57⁺ TEMRA in both cohorts (P < 0.001). In KTx, increased frequency of CD57⁺KLRG1⁺ were associated with viremia control (P = 0.05). In LTx, frequency > median of CD57⁺KLRG1⁺ conferred a 67 % reduced risk for CLAD or death (95 % CI; 3-89 % P = 0.04). CD57⁺KLRG1⁺ TEMRA showed evidence of cytotoxic and effector function, whereas CD57^-KLRG1⁺ TEMRA showed evidence of exhaustion. CD57⁺KLRG1⁺ TEMRA were most active against CMV and reduced risk for viremia in KTx and CLAD in LTx. This population merits increased attention for its potential role in mediating CMV-associated transplant outcomes.