Chronic allograft rejection. Do the Th2 cells preferentially induced by indirect alloantigen recognition play a dominant role?
Chronic allograft rejection. Do the Th2 cells preferentially induced by indirect alloantigen recognition play a dominant role?
复制标题
慢性同种异体移植排斥反应。
DOI：
10.1097/00007890-199909270-00001
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发表时间：
1999
期刊：
影响因子：
6.2
通讯作者：
Shirwan,H
中科院分区：
文献类型：
--
作者：
Shirwan,H
慢性排斥反应已成为临床上影响同种异体移植物长期存活的主要障碍。虽然这种排斥反应的病因是多因素的，同种异体抗原特异性免疫激活起着最关键的作用。我们在此假设，CD 4 + Th 2细胞，优先诱导的间接识别同种异体组织相容性抗原移植后期可能发挥最关键的作用，在启动和/或维持慢性同种异体移植排斥反应。用于预防急性排斥反应的免疫抑制和移植物中抗原呈递细胞和同种配体的性质都可能导致免疫偏离Th 2应答。这种反应可能进一步延续2型细胞因子，可以想象产生的活化的巨噬细胞，NK细胞，和CD 8 + T细胞在移植物。由这种2型反应诱导的细胞因子和生长因子进而激活B细胞、内皮细胞和平滑肌细胞，这些细胞通过产生间质纤维化、细胞外基质沉积和血管新生内膜增生所需的同种抗体和生长激素，共同促成慢性同种异体移植物排斥的发病机制。
Chronic rejection has been the major obstacle to the long-term allograft survival in the clinic. Although the etiology of this rejection reaction is multifactorial, alloantigen-specific immune activation plays the most critical role. We herein hypothesize that CD4+ Th2 cells that are preferentially induced by the indirect recognition of allogeneic histocompatibility antigens late in transplantation may play the most critical role in the initiation and/or maintenance of chronic allograft rejection. Immunosuppression used to prevent acute rejection and the nature of antigen-presenting cells and alloligands in the graft may all contribute to immune deviation to the Th2 response. This response may be further perpetuated by type 2 cytokines conceivably produced by activated macrophages, NK cells, and CD8+ T cells in the graft. Cytokines and growth factors induced by this type 2 response, in turn, allow for activation of B, endothelial, and smooth muscle cells that collectively contribute to the pathogenesis of chronic allograft rejection by producing alloantibodies and growth hormones required for interstitial fibrosis, extracellular matrix deposition, and vascular neointimal hyperplasia.