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2017 ; 14
(4
): 2817-2822
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Triptolide inhibits CD4(+) memory T cell-mediated acute rejection and prolongs
cardiac allograft survival in mice
#MMPMID28912844
Qiu S
; Lv D
Exp Ther Med
2017[Oct]; 14
(4
): 2817-2822
PMID28912844
show ga
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-? (IFN-?), IL-10 and transforming growth factor ?1 (TGF-?1) 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-? secretion
(P<0.01), significantly increase TGF-?1 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.