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Age‐related effects on thymic output and homeostatic T cell expansion following depletional induction in renal transplant recipients
Author(s) -
Xu He,
Lee HuiJie,
Schmitz Robin,
Shaw Brian I.,
Li Shu,
Kirk Allan D.
Publication year - 2021
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/ajt.16625
Subject(s) - alemtuzumab , immunology , homeostasis , t cell , medicine , belatacept , cell growth , transplantation , immunosuppression , biology , kidney transplantation , immune system , kidney transplant , genetics
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 (T Naïve ) cells emerged posttransplantation. Analysis by generalized estimating equation linear models revealed a strong negative linear association between reconstituting T Naïve 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. Trial Registration: ClinicalTrials.gov ‐ NCT00565773.