Jungraithmayr W, Ji L, Yang L, Weder W, Korom S, Hersberger M
Division of Thoracic Surgery, University Hospital Zurich, Zurich, Switzerland.
Transplant Proc. 2009 Dec;41(10):4316-20. doi: 10.1016/j.transproceed.2009.08.057.
Acute allograft rejection (AR) remains a major problem in solid organ transplantation. The pivotal mechanism hinges on alloantigen recognition by recipient T helper (T(h)) cells that differentiate into T(h)1 and T(h)2. This study investigated the association of mRNA levels of the transcription factors T-box expressed in T cells and GATA-binding protein 3 with the development of T(h)1/T(h)2-directed immune responses. We investigated the expression of T-bet and GATA-3 mRNA levels and the protein levels of their marker cytokines interleukin (IL)-2 and IL-4 in orthotopically transplanted rat lungs during AR. We observed a nonsignificant increase in T-bet expression following allografting at days 3 and 5 but there was a significant reduction in GATA-3 expression on day 5 compared with controls. The ratio of T-bet to GATA-3 expression showed a trend to increase at day 3 following allografting reaching significance at 5 days. These changes were associated with a significant increase in the expression of IL-2 over IL-4 on days 3 and 5. This study suggests that T(h)1 responses play a major role during AR in the rat lung, and that this differentiation can be monitored by measuring mRNA levels of T-bet and GATA-3.
急性同种异体移植排斥反应（AR）仍然是实体器官移植中的一个主要问题。关键机制取决于受体T辅助（Th）细胞对同种异体抗原的识别，这些细胞分化为Th1和Th2。本研究调查了T细胞中表达的转录因子T-box和GATA结合蛋白3的mRNA水平与Th1/Th2定向免疫反应发展之间的关联。我们研究了原位移植大鼠肺在AR期间T-bet和GATA-3 mRNA水平的表达以及其标志性细胞因子白细胞介素（IL）-2和IL-4的蛋白水平。我们观察到移植后第3天和第5天T-bet表达有不显著的增加，但与对照组相比，第5天GATA-3表达有显著降低。移植后第3天T-bet与GATA-3表达的比值呈增加趋势，在第5天达到显著水平。这些变化与第3天和第5天IL-2表达相对于IL-4显著增加有关。本研究表明，Th1反应在大鼠肺AR期间起主要作用，并且这种分化可以通过测量T-bet和GATA-3的mRNA水平来监测。
