CMV-specific T cell dynamics revealed by immune profiling in kidney transplant recipients

Objectives: Cytomegalovirus (CMV) remains a major cause of morbidity following kidney transplantation (KT). We applied flow-cytometric phenotyping and activation-induced marker (AIM) assays to characterize immune reconstitution and CMV-specific T cell signatures after KT and assess whether early AIM responses predict clinically significant CMV infection (CS-CMVi). Methods: : 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, 9, and 12 months. CS-CMVi was defined as CMV infection requiring antiviral therapy. Results: : 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 predicted 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. Conclusion: Early CMV-specific CD4 + /CD8 + imbalances measured by AIM are associated with CS-CMVi. These findings support the prospective evaluation of CMV-AIM assays as a precision immune-monitoring tool in larger prospective studies.