AUTHOR=Bellier Lucas Milo , Kaminski Hannah , Merville Pierre , Couzi Lionel TITLE=Interactions Between Immunosuppressive Regimens and Cytomegalovirus Infection After Solid-Organ Transplantation JOURNAL=Transplant International VOLUME=Volume 39 - 2026 YEAR=2026 URL=https://www.frontierspartnerships.org/journals/transplant-international/articles/10.3389/ti.2026.15987 DOI=10.3389/ti.2026.15987 ISSN=1432-2277 ABSTRACT=Cytomegalovirus (CMV) remains a major infectious complication after solid-organ transplantation, driven by immunosuppressive therapies that alter CMV-specific cell-mediated immunity. Antithymocyte globulin induces profound and prolonged T-cell depletion, transiently impairing CMV-specific cell-mediated immunity and increasing CMV risk in seropositive recipients. Calcineurin inhibitors suppress cytokine production, notably IL-2 and IFN-γ, without significantly impairing cytotoxic function, while mycophenolate mofetil limits lymphocyte proliferation but preserves effector capacity. In contrast, mTOR inhibitors exert dual antiviral and immunomodulatory effects by directly inhibiting CMV replication and enhancing CMV-specific T-cell memory formation. Belatacept, through CD28–CD80/CD86 blockade, may predispose to late, severe, or relapsing CMV disease, particularly in elderly or D+/R− recipients. Corticosteroids broadly inhibit NK cell cytotoxicity and CMV-specific T-cell responses, but clinical data on steroid withdrawal remain inconsistent. Overall, CMV risk is determined less by a single drug than by the cumulative depth of immunosuppression. Integrating immune monitoring tools, such as CMV-specific T-cell assays, could enable tailored immunosuppressive regimens balancing antiviral protection with graft survival.