Early CMV-specific T cell immune reconstitution after kidney transplantation: A prospective AIM-based cohort study

Cytomegalovirus (CMV) remains a major cause of morbidity following kidney transplantation (KT). We applied flow cytometry-based phenotyping and activation-induced marker (AIM) assays to characterize early immune reconstitution and CMV-specific T-cell dynamics after KT and to determine whether early AIM responses are associated with clinically significant CMV infection (CS-CMVi).

Twenty-nine adult KT recipients were followed prospectively for 12 months: 13 donor CMV-positive/recipient CMV-negative (D⁺/R^-) and 16 CMV-seropositive recipients (R⁺). CMV-specific CD4⁺ and CD8⁺ T cells were quantified by AIM assay at 2 weeks and at 3, 6, 9, and 12 months. CS-CMVi was defined as CMV infection requiring antiviral therapy.

Immune reconstitution featured expansion of CD4⁺ TEMRA and Th1-like cells with contraction of Th2/Th17 subsets. Seven recipients (24%) developed CS-CMVi, including five D+/R-. Early CD4⁺-predominant CMV-specific responses shifted toward CD8⁺ expansion with viral replication. At 2 weeks, the CMV-specific CD4⁺: CD8⁺ ratio was associated with CS-CMVi (AUC 0.83, p = 0.012); a cut-off ≥1.37 yielded 86% sensitivity and 71% specificity. After 6 months, CMV serostatus shaped Th-cell activation, with R⁺ recipients showing greater Th1/Treg and reduced Th2/Th17 responsiveness.

Early CMV-specific CD4⁺/CD8⁺ imbalances measured by AIM are associated with CS-CMVi and reflect distinct trajectories of immune reconstitution after KT. These findings support prospective evaluation of CMV-AIM assays as precision immune-monitoring tools in larger studies.