Premature senescence of T cells in long-term survivors of renal transplantation

Autor: Ping Li, Li Liu, Nan Ge, Dawei Xu, Hongwei Wang, Magnus Björkholm, Fenglan Lou, Chuan Tian
Rok vydání: 2011
Předmět:
Zdroj: Biochemical and Biophysical Research Communications. 407:599-604
ISSN: 0006-291X
Popis: Prevention of graft rejection in renal transplant recipients depends on chronic treatment with immunosuppressive agents. However, impaired immune functions and immunosurveillance may cause infection, cancer and many other problems, which subsequently compromise quality of life and survival of patients. In the present study, we assessed potential premature immune-senescence in long-term survivors of kidney transplant patients receiving immunosuppressive agents. Peripheral blood lymphocytes derived from patients had significantly shorter telomeres than those from age- and sex-matched healthy individuals. Consistent with this, lower expression of telomerase reverse transcriptase (hTERT) and telomerase activity was observed in patients' lymphocytes. The level of p16(ink4A) expression was elevated in patients' cells. Moreover, the CD8(+)/CD28(-) fraction of late-stage differentiated T cells was significantly increased in the patients. In vitro studies further showed that cyclosporine A, a widely used immunosuppressive drug in transplant patients, attenuated induction of hTERT and telomerase activation in T cells treated with the mitogenic agent concanavalin A. Taken together, immunosuppressant-mediated premature senescence of T lymphocytes occurs in renal transplant recipients.
Databáze: OpenAIRE