Universidade Federal do Rio Grande do Sul, Division of Nephrology, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
Transpl Immunol. 2012 Jan;26(1):1-10. doi: 10.1016/j.trim.2011.08.009. Epub 2011 Sep 13.
Naturally occurring and induced regulatory T cells (Tregs) can become hyporesponsive and anergic to antigen stimulation in autoimmune diseases and allograft rejection. The mechanisms of suppression of effector T cells by Tregs remain unclear, but there are in vitro and in vivo evidences showing that these cells are able to suppress antigen-specific responses via direct cell-to-cell contact, secrete anti-inflammatory cytokines such as TGF-β and IL-10, and inhibit the generation of memory T cells, among others. The transcription factor FOXP3 is a specific marker of Tregs and its deficiency is associated with autoimmune diseases and inflammation. During acute rejection of kidney allografts, an augmented FOXP3 gene expression as well as increased CD4(+)CD25(+)FOXP3(+) and other cell populations are observed in graft biopsies. However, it is not clear whether Tregs migrate into the graft and are retained there to suppress the inflammatory process, or whether they are directly associated with more complex mechanisms to induce immune tolerance. FOXP3(+) Tregs may direct the immune response toward a graft acceptance program, potentially affecting the long-term survival of transplanted organs and tissues. Immunosuppressive drugs modulate the number and function of circulating Tregs and FOXP3 expression. Experimental and clinical studies have shown that mTOR inhibitors have positive and calcineurin inhibitors negative effects on Tregs, but it is difficult to set apart the effect of multiple other factors known to be associated with short- and long-term renal graft outcomes. This review aimed to describe the functions of Tregs and its transcription factor FOXP3 in suppression of immune response during rejection and in induction of kidney graft tolerance, as well as to review the individual effects of immunosuppressive drugs on Tregs.
在自身免疫性疾病和同种异体移植物排斥中，天然存在和诱导的调节性 T 细胞 (Treg) 可能对抗原刺激反应迟钝和无能。Treg 抑制效应 T 细胞的机制尚不清楚，但有体外和体内证据表明，这些细胞能够通过直接细胞接触抑制抗原特异性反应，分泌 TGF-β 和 IL-10 等抗炎细胞因子，并抑制记忆 T 细胞的产生等。转录因子 FOXP3 是 Treg 的特异性标志物，其缺乏与自身免疫性疾病和炎症有关。在肾同种异体移植物急性排斥反应中，在移植物活检中观察到 FOXP3 基因表达增加，以及 CD4(+)CD25(+)FOXP3(+)和其他细胞群增加。然而，尚不清楚 Treg 是否迁移到移植物中并保留在那里以抑制炎症过程，或者它们是否与更复杂的诱导免疫耐受机制直接相关。FOXP3(+)Treg 可能将免疫反应引导至移植物接受程序，潜在地影响移植器官和组织的长期存活。免疫抑制剂调节循环 Treg 的数量和功能以及 FOXP3 的表达。实验和临床研究表明，mTOR 抑制剂对 Treg 具有积极作用，而钙调神经磷酸酶抑制剂具有消极作用，但很难将其与已知与短期和长期肾移植物结局相关的其他多个因素的影响区分开来。本综述旨在描述 Treg 及其转录因子 FOXP3 在排斥反应期间抑制免疫反应和诱导肾移植物耐受中的作用，并综述免疫抑制剂对 Treg 的单独作用。
