Age-related effects on thymic output and homeostatic T cell expansion following depletional induction in renal transplant recipients.
Am J Transplant
; 21(9): 3163-3174, 2021 09.
Article
em En
| MEDLINE
| ID: mdl-33942491
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: ClinicalTrials.gov - NCT00565773.
Palavras-chave
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
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Limite:
Humans
/
Middle aged
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article