Yang C P, McDonagh M, Bell E B
Immunology Research Group, School of Biological Sciences, University of Manchester, Medical School, United Kingdom.
Transplantation. 1995 Jul 27;60(2):192-9.
The ability of preoperative blood transfusion to extend the survival of organ allografts is well known but poorly understood. To study this phenomenon, adult PVG (RT1c) rats were rendered tolerant of DA (RT1a) cardiac allografts by prior donor-specific blood transfusion (DST). We investigated the cellular basis of the transfusion effect by adoptively transferring CD4 T cell subsets, obtained from thoracic duct lymph of tolerant rats, into cardiac allografted athymic PVG nude recipients. Surprisingly, CD4 T cells from DST rats evoked acute rejection on adoptive transfer. Evidence indicated that CD8 T cells played no role in DST-induced tolerance. Analysis of CD4 T cell subsets, defined in the rat by mAb OX22 (anti-CD45RC), revealed an unusual pattern of responsiveness. CD45RC+ CD4 T cells (normally capable of inducing prompt rejection), when obtained from rats given a specific blood transfusion, were depleted of alloreactive cells and deficient at inducing rejection. In contrast, the CD45RC- subset (normally slow at evoking graft destruction) was highly active and ten-fold-enriched in its ability to induce rejection. Destruction of cardiac allografts by this latter subset was, however, completely inhibited by giving nude recipients a specific (but not a third-party) blood transfusion two weeks before heart grafting and cell transfer. Apparently, tolerance was maintained by residual elements of the prior blood transfusion that prevented the specific CD45RC- subset from regaining an alloaggressive capacity.
术前输血可延长器官同种异体移植存活时间的能力已为人熟知，但人们对此了解甚少。为研究这一现象，通过预先进行供体特异性输血（DST），使成年PVG（RT1c）大鼠对DA（RT1a）心脏同种异体移植产生耐受。我们通过将从耐受大鼠胸导管淋巴中获得的CD4 T细胞亚群过继转移到心脏同种异体移植的无胸腺PVG裸鼠受体中，研究了输血效应的细胞基础。令人惊讶的是，来自DST大鼠的CD4 T细胞在过继转移时引发了急性排斥反应。有证据表明，CD8 T细胞在DST诱导的耐受中不起作用。用单克隆抗体OX22（抗CD45RC）对大鼠CD4 T细胞亚群进行分析，发现了一种不同寻常的反应模式。当从接受特异性输血的大鼠中获得时，CD45RC + CD4 T细胞（通常能够迅速诱导排斥反应）的同种异体反应性细胞减少，诱导排斥反应的能力不足。相比之下，CD45RC - 亚群（通常引发移植物破坏的速度较慢）高度活跃，其诱导排斥反应的能力提高了十倍。然而，在心脏移植和细胞转移前两周给裸鼠受体进行特异性（而非第三方）输血，可完全抑制后一个亚群对心脏同种异体移植的破坏。显然，先前输血的残余成分维持了耐受状态，阻止了特异性CD45RC - 亚群恢复同种异体攻击能力。
