Background: CD4 T cell reconstitution after antithymocytes globulins (ATG) is dependent on pre-transplant thymic function and persistent ATG-induced CD4 T cell lymphopenia is associated with abnormalities close to those observed in immune senescence. We hypothesized that ATG could be responsible of accelerated immune senescence in renal transplant recipients (RTR).

Methods: We analyzed a prospective cohort of 66 incident RTR. Thymic output of recent thymic emigrants (RTE), regulatory T cells (Treg), CD8+ T cell subsets were studied by flow cytometry at transplant and one year after transplantation. Thirty out of 66 patients were also studied for T lymphocyte relative telomere length and telomerase activity at both times. Age, gender, induction therapy (ATG or anti-CD25 monoclonal antibody [mAb]), immunosuppressive regimen, and CMV status were analysed as potential confounding factors.

Results: 46 patients received ATG whereas 20 received monoclonal anti-CD25 mAb. Pre-transplant RTE cell count predicted CD4+ T cell count 1 year after transplantation. RTE cell count significantly decreased and was lower in ATG than in anti-CD25 mAb-treated recipients. Proportion of CD8+CD28-T cells increased after transplant in ATG patients. This increase was more pronounced in RTR with an inverted CD4/CD8 T-cell ratio and in CMV-positive RTR. Treg were more frequent after transplant in ATG than in anti-CD25 mAb recipients. In ATG recipients, Treg peripheral expansion was related to poor thymic function one year post-transplant. RTL and RTA increased in anti-CD25 mAb but not in ATG recipients one year post-transplant.

Conclusions: ATG is associated with reduced thymic output of naive T cells, increased Treg, lymphocyte phenotype, RTL and RTA evocative of immune senescence. Mechanisms and clinical consequences remain to be studied.

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