Triptolide inhibits CD4+ memory T cell-mediated acute rejection and prolongs cardiac allograft survival in mice

摘要

There have been numerous investigations into the immunosuppressive effects of triptolide; however, its inhibitory effects on memory T cells remain to be elucidated. Using a cluster of differentiation (CD)4⁺ memory T-cell transfer model, the aim of the present study was to determine the inhibitory effects of triptolide on CD4⁺ memory T cell-mediated acute rejection and to determine the potential underlying mechanisms. At 4 weeks after skin transplantation, mouse cervical heart transplantation was performed following the transfer of CD4⁺ memory T cells. Mice were divided into two groups: A Control [normal saline, 30 ml/kg/day; intraperitoneal injection (ip)] and a triptolide group (triptolide, 3 mg/kg/day; ip). Graft survival, pathological examination and the corresponding International Society for Heart & Lung Transplantation (ISHLT) scores were assessed 5 days following heart transplantation, and levels of interleukin (IL)-2, interferon-γ (IFN-γ), IL-10 and transforming growth factor β1 (TGF-β1) in cardiac grafts and peripheral blood were assessed using reverse transcription-quantitative polymerase chain reaction and ELISA. The duration of cardiac graft survival in the triptolide group was significantly increased compared with the control group (14.3±0.4 vs. 5.3±0.2 days; P<0.001). Further pathological examinations revealed that the infiltration of inflammatory cells and myocardial damage in the cardiac grafts was notably reduced by triptolide, and the corresponding ISHLT scores in the triptolide group were significantly lower than those of the control group (grade 2.08±0.15 vs. 3.67±0.17; P<0.001). In addition, triptolide was able to significantly reduce IL-2 and IFN-γ secretion (P<0.01), significantly increase TGF-β1 secretion in the cardiac grafts and peripheral blood (P<0.01) and increase IL-10 secretion in the cardiac grafts. Therefore, the present study suggests that triptolide inhibits CD4⁺ memory T cell-mediated acute rejection and prolongs cardiac allograft survival in mice. This effect may be mediated by the inhibition of cytokine secretion by type 1 T helper cells and promotion of regulatory T cell proliferation.