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Age‐related effects on thymic output and homeostatic T cell expansion following depletional induction in renal transplant recipients

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Thymic output and homeostatic mature cell proliferation both influence T cell repopulation following depletional induction, though the relative contribution of each and their association with recipient age have not been… Click to show full abstract

Thymic output and homeostatic mature cell proliferation both influence T cell repopulation following depletional induction, though the relative contribution of each and their association with recipient age have not been well studied. We investigated the repopulating T cell kinetics in kidney transplant recipients who underwent alemtuzumab induction followed by belatacept/rapamycin‐based immunosuppression over 36‐month posttransplantation. We focused specifically on the correlation between repopulating T cell subsets and the age of patients. Substantial homeostatic Ki67‐expressing T cell proliferation was seen posttransplantation. A repertoire enriched for naïve T (TNaïve) cells emerged posttransplantation. Analysis by generalized estimating equation linear models revealed a strong negative linear association between reconstituting TNaïve cells and advancing age. A relationship between age and persistence of effector memory cells was shown. We assessed thymic output and found an increase in the frequency of recent thymic emigrants (RTEs, CD4+CD31+) at 12‐month posttransplantation. Patients under 30 years of age showed significantly higher levels of CD4+CD31+ cells than patients over 55 years of age pre‐ and posttransplantation. IL‐7 and autologous mature dendritic cells (mDCs) induced CD57− cell proliferation. In contrast, mDCs, but not IL‐7, induced CD57+ cell proliferation. This study establishes the relationship between age and thymic output during T cell homeostatic repopulation after alemtuzumab induction.

Keywords: thymic output; age; induction; posttransplantation; cell

Journal Title: American Journal of Transplantation
Year Published: 2021

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