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

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 p16ink4A 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.

► T cell aging occurs in renal transplant recipients.
► CysA inhibits telomerase expression.
► Immunosuppressive agents cause premature immunosenescence.