Steger Ulrich, Kingsley Cherry I, Karim Mahzuz, Bushell Andrew R, Wood Kathryn J
Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
Transplantation. 2006 Nov 15;82(9):1202-9. doi: 10.1097/01.tp.0000235913.58337.b4.
Liver grafts transplanted across a major histocompatibility barrier are accepted spontaneously and induce donor specific tolerance in some species. Here, we investigated whether liver allograft acceptance is characterized by, and depends upon, the presence of donor reactive CD25CD4 regulatory T cells.
CD25 and CD25CD4 T cells, isolated from CBA. Ca (H2) recipients of C57BL/10 (B10; H2) liver and heart allografts 10 days after transplantation, were transferred into CBA. Rag1 mice to investigate their influence on skin allograft rejection mediated by CD45RBCD4 effector T Cells.
Fully allogeneic B10 liver allografts were spontaneously accepted by naive CBA.Ca recipient mice, whereas B10 cardiac allografts were acutely rejected (mean survival time=7 days). Strikingly, however, CD25CD4 T cells isolated from both liver and cardiac allograft recipients were able to prevent skin allograft rejection in this adoptive transfer model. Interestingly, CD25CD4 T cells isolated from liver graft recipients also showed suppressive potency upon adoptive transfer. Furthermore, depletion of CD25CD4 T cells in primary liver allograft recipients did not prevent the acceptance of a secondary donor-specific skin graft.
Our data provide evidence that the presence of CD25CD4 regulatory T cells is not a unique feature of allograft acceptance and is more likely the result of sustained exposure to donor alloantigens in vivo.
跨越主要组织相容性屏障移植的肝移植物可被自发接受，并在某些物种中诱导供体特异性耐受。在此，我们研究了肝同种异体移植的接受是否以供体反应性CD25⁺CD4⁺调节性T细胞的存在为特征并依赖于该细胞的存在。
从移植后10天的C57BL/10（B10；H2）肝和心脏同种异体移植的CBA.Ca受体中分离出CD25⁺和CD25⁺CD4⁺T细胞，将其转移到CBA.Rag1小鼠中，以研究它们对由CD45RB⁺CD4⁺效应T细胞介导的皮肤同种异体移植排斥反应的影响。
完全同种异体的B10肝同种异体移植被未致敏的CBA.Ca受体小鼠自发接受，而B10心脏同种异体移植则被急性排斥（平均存活时间=7天）。然而，引人注目的是，从肝和心脏同种异体移植受体中分离出的CD25⁺CD4⁺T细胞在这种过继转移模型中能够预防皮肤同种异体移植排斥反应。有趣的是，从肝移植受体中分离出的CD25⁺CD4⁺T细胞在过继转移时也表现出抑制能力。此外，原发性肝同种异体移植受体中CD25⁺CD4⁺T细胞的耗竭并不能阻止二次供体特异性皮肤移植物的接受。
我们的数据提供了证据，表明CD25⁺CD4⁺调节性T细胞的存在不是同种异体移植接受的独特特征，更可能是体内持续暴露于供体同种异体抗原的结果。
