Anti-thymocyte globulin-mediated immunosenescent alterations of T cells in kidney transplant patients

Abstract

ObjectivesKidney transplant (KT) is the most effective treatment for end-stage renal disease. The immunosuppressant anti-thymocyte globulin (ATG) has been applied for induction therapy to reduce the risk of acute transplant rejection for patients at high immunological risk. Despite its putative role in replicative stress during immune reconstitution, the effects of ATG on T-cell immunosenescent changes remain to be understood. MethodsPhenotypic and functional features of senescent T cells were examined by flow cytometry in 116 healthy controls (HC) and 95 KT patients for comparative analysis according to ATG treatment and CMV reactivation. The TCR repertoire was analysed in peripheral blood mononuclear cells (PBMCs) of KT patients. ResultsT cells of KT patients treated with ATG (ATG(+)) show typical immunosenescent features, accumulation of CD28(-), CD85j(+) or CD57(+) T cells, and imbalance of functional T-cell subsets, compared with untreated KT patients (ATG(-)). Plasma IL-15 and CMV-IgG levels were higher in KT patients than in HCs, and the IL-15 level positively correlated with the frequency of CD28(-) T cells in KT patients. ATG(+) patients had a higher prevalence of CMV reactivation, which is associated with an increased frequency of CD28(-) T cells. As a result, ATG(+) patients had expanded CMV-specific T cells and decreased TCR diversity. However, proliferation, cytokine-producing capacity and polyfunctionality of T cells were preserved in ATG(+) patients. ConclusionOur findings suggest that ATG treatment contributes to the accumulation of senescent T cells, which may have lifelong clinical implications in KT patients. Thus, these patients require long-term and comprehensive immune monitoring.