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

He Xu*, Hui Jie Lee, Robin Schmitz, Brian I. Shaw, Shu Li, Allan D. Kirk*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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. Trial Registration: - NCT00565773.

Original languageEnglish
Pages (from-to)3163-3174
Number of pages12
JournalAmerican Journal of Transplantation
Issue number9
StatePublished - Sep 2021
Externally publishedYes


  • basic (laboratory) research/science
  • clinical research/practice
  • immunobiology
  • immunosuppressant - fusion proteins and monoclonal antibodies: alemtuzumab
  • immunosuppressant - fusion proteins and monoclonal antibodies: belatacept
  • immunosuppression/immune modulation
  • immunosuppressive regimens - induction
  • kidney transplantation/nephrology
  • lymphocyte biology: differentiation/maturation
  • lymphocyte biology: proliferation


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