Hall Bruce M, Plain Karren M, Verma Nirupama D, Tran Giang T, Boyd Rochelle, Robinson Catherine M, Nicolls Mark R, Berger Manuela E, Nomura Masaru, Hodgkinson Suzanne J
Immune Tolerance Laboratory, University of New South Wales, Australian Technology Park, New South Wales, Australia.
Transplantation. 2007 Apr 27;83(8):1075-84. doi: 10.1097/01.tp.0000259553.66185.2f.
The mechanisms by which CD4+T cells, especially CD4+ CD25+T cells, transfer allograft specific tolerance are poorly defined. The role of cytokines and the effect on antigen-presenting cells is not resolved.
Anti-CD3 monoclonal antibody (mAb) therapy induced tolerance to PVG heterotopic cardiac transplantation in DA rats. Peripheral CD4+T cells or CD4+ CD25+ and CD4+ CD25-T cell subsets were adoptively transferred to irradiated DA hosts grafted with PVG heart grafts. For specificity studies, tolerant CD4+T cells were transferred to hosts with Lewis or (PVGxLewis)F1 heart grafts. Cytokine mRNA induction and the requirement for interleukin (IL)-4 and transforming growth factor (TGF)-beta in the transfer of tolerance was assessed.
CD4+T cells transferred specific tolerance and suppressed naïve CD4+T cells capacity to effect rejection of PVG but not Lewis grafts. (PVGxLewis)F1 grafts had a major rejection episode but recovered. Later these hosts accepted PVG but not Lewis skin grafts. Adoptive hosts restored with tolerant or naïve cells had similar levels of mRNA expression for all Th1 and Th2 cytokines and effector molecules assayed. Transfer of tolerance by CD4+T cells was not blocked by mAb to IL-4 or TGF-beta. CD4+ CD25-T cells from either naïve or tolerant hosts effected rejection. In contrast neither tolerant nor naïve CD4+ CD25+T cells restored rejection.
Specific tolerance transfer required CD4+ containing CD4+ CD25+T cells. An inflammatory response with induction of mRNA for Th1 and Th2 cytokines plus cytotoxic effector molecules occurred, but IL-4 and TGF-beta were not essential. Inhibition of antigen presenting cells was not the sole mechanism as there was no linked tolerance.
CD4+T细胞，尤其是CD4+CD25+T细胞传递同种异体移植特异性耐受的机制尚不清楚。细胞因子的作用以及对抗抗原呈递细胞的影响尚未明确。
抗CD3单克隆抗体（mAb）疗法诱导DA大鼠对PVG异位心脏移植产生耐受。将外周CD4+T细胞或CD4+CD25+和CD4+CD25-T细胞亚群过继转移至移植了PVG心脏移植物的经照射的DA宿主。为进行特异性研究，将耐受的CD4+T细胞转移至移植了Lewis或（PVG×Lewis）F1心脏移植物的宿主。评估细胞因子mRNA的诱导情况以及耐受转移过程中白细胞介素（IL）-4和转化生长因子（TGF）-β的需求。
CD4+T细胞传递特异性耐受，并抑制了幼稚CD4+T细胞对PVG移植物而非Lewis移植物产生排斥反应的能力。（PVG×Lewis）F1移植物发生了一次主要排斥反应，但随后恢复。之后这些宿主接受了PVG皮肤移植物，但不接受Lewis皮肤移植物。用耐受或幼稚细胞重建的过继宿主中，所检测的所有Th1和Th2细胞因子及效应分子的mRNA表达水平相似。CD4+T细胞介导的耐受转移未被抗IL-4或TGF-β的单克隆抗体阻断。来自幼稚或耐受宿主的CD4+CD25-T细胞引发排斥反应。相反，耐受或幼稚的CD4+CD25+T细胞均未恢复排斥反应。
特异性耐受转移需要含有CD4+CD25+T细胞的CD4+细胞。出现了Th1和Th2细胞因子以及细胞毒性效应分子mRNA诱导的炎症反应，但IL-4和TGF-β并非必需。对抗抗原呈递细胞的抑制并非唯一机制，因为不存在连锁耐受。
