Abstract
Abstract Cytomegalovirus (CMV) infection is a significant contributor to both immune aging and complications after solid organ transplantation. A major mediator of both effects is viral reactivation, in which latent CMV in the host undergoes new replication requiring immune control. Immunocompetent CMV seropositive individuals display hallmarks of CD8 T cell aging earlier than CMV seronegative individuals, including shortened telomeres, defects in proliferation and signaling, and altered cytokine production. In the context of transplantation, immunosuppression impairs immune control, leading to negative impacts including late-term graft loss. We hypothesized that T cell aging is accelerated after transplant in CMV+ individuals, regardless of detectable viral reactivation. To address this hypothesis, we measured telomere length and conducted phenotyping through flow cytometry and targeted single cell RNA sequencing. We found a statistical increase in CD57 expression which correlated with a trend towards decreased telomere length in the first year after transplantation. We found that CD57+ CD8 T cells expanded in the first year after transplantation specifically in CMV+ recipients. We also found that clonal expansion was associated with a terminally differentiated phenotype, defined as CD45RA+ CD27− CCR7−. Overall, our data demonstrate an enhanced aging phenotype in the first year post-transplant in CMV seropositive individuals, based on CD57+ expression and terminal differentiation. These findings suggest that CD8 T cell aging may be an important factor to understanding immunity in transplant recipients.