Tay Szun Szun, Plain Karren M, Bishop G Alex
Collaborative Transplantation Laboratory, Bosch Institute, Royal Prince Alfred Hospital and University of Sydney, Australia.
Curr Opin Organ Transplant. 2009 Feb;14(1):16-22. doi: 10.1097/MOT.0b013e32831ebdf5.
Due to the dominance of Th1 cytokines in rejection and the ability of Th2 cytokines, particularly IL-4, to inhibit Th1 responses, it has long been held that Th2 cytokines can improve transplant outcomes. Although there is some support for this, there is mounting evidence that IL-4 and Th2 cytokines can promote graft dysfunction. These disparate effects are reviewed.
The role of Th2 cytokines in graft dysfunction is not necessarily due to promotion of humoral immunity, but is due to their ability to drive T-cell and non-T-cell responses including alternative activation of macrophages. Alternatively, activated macrophages compete with classically activated macrophages for arginine and they are mutually exclusive, analogous to mutual competition between Th1 and Th2 cells. Recent findings also point to two subsets of regulatory T cells (Tregs), each dependent on either Th1 or Th2 cytokines. In addition to its effects on bone marrow-derived cells, IL-4 affects parenchymal cells by signalling through the type II receptor, which consists of the IL-4R alpha chain (IL-4Ralpha) and the IL-13Ralpha1, which also binds IL-13.
The effects of Th2 cytokines in transplantation depend on their cellular targets, the timing and form of administration and on Th2 cytokine-dependent Tregs.
由于Th1细胞因子在排斥反应中占主导地位，且Th2细胞因子（尤其是IL-4）具有抑制Th1反应的能力，长期以来人们一直认为Th2细胞因子可改善移植结局。尽管有一些证据支持这一点，但越来越多的证据表明IL-4和Th2细胞因子可促进移植物功能障碍。本文对这些不同的效应进行综述。
Th2细胞因子在移植物功能障碍中的作用不一定是由于促进体液免疫，而是由于它们驱动T细胞和非T细胞反应的能力，包括巨噬细胞的替代性激活。此外，活化的巨噬细胞与经典活化的巨噬细胞竞争精氨酸，它们相互排斥，类似于Th1和Th2细胞之间的相互竞争。最新发现还指出了调节性T细胞（Tregs）的两个亚群，每个亚群分别依赖于Th1或Th2细胞因子。除了对骨髓来源细胞的作用外，IL-4还通过II型受体发出信号影响实质细胞，该受体由IL-4Rα链（IL-4Ralpha）和也结合IL-13的IL-13Ralpha1组成。
Th2细胞因子在移植中的作用取决于它们的细胞靶点、给药时间和形式以及依赖Th2细胞因子的Tregs。
