Alloreactive T cell responses and acute rejection of single class II MHC-disparate heart allografts are under strict regulation by CD4+CD25+ T cells
Alloreactive T cell responses and acute rejection of single class II MHC-disparate heart allografts are under strict regulation by CD4+CD25+ T cells
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DOI：
10.4049/jimmunol.174.6.3741
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发表时间：
2005-03-15
影响因子：
4.4
通讯作者：
Fairchild, RL
中科院分区：
文献类型：
--
作者：
Schenk, S;Kish, DD;Fairchild, RL
来自B6.H-2（bm 12）小鼠的皮肤而非血管化的心脏同种异体移植物被C57 BL/6受体急性排斥，以响应单一的II类MHC差异。本研究探讨了B6.H-2（bm 12）受体C57 BL/6心脏移植急性排斥反应的预防机制。B6.H-2（bm 12）心脏同种异体移植物在C57 BL/6受体中诱导低水平的同种异体反应性效应T细胞引发，并且这种引发伴随着低水平的细胞浸润到同种异体移植物中并迅速消退。长期存活的心脏移植受体不能排斥B6.H-2（bm 12）皮肤移植物，这表明心脏移植物诱导的潜在下调机制。C57 BL/6受体CD 25（+）细胞的耗竭导致同种异体反应性T细胞引发和B6.H-2（bm 12）心脏移植物的急性排斥反应增加15倍。同样，只有当CD 25（+）细胞耗尽时，B6.Rag（-/-）受体与野生型C57 BL/6脾细胞的重建才会导致B6.H-2（bm 12）心脏移植物的急性排斥反应。这些结果表明，C57 BL/6受体对单一II类MHC-不同B6.H-2（bm 12）心脏同种异体移植物的急性排斥反应受到了CD 25（+）调节细胞的抑制，这些细胞限制了同种异体反应性T细胞的克隆扩增。
Skin but not vascularized cardiac allografts from B6.H-2(bm12) mice are acutely rejected by C57BL/6 recipients in response to the single class II MHC disparity. The underlying mechanisms preventing acute rejection of B6.H-2(bm12) heart allografts by C57BL/6 recipients were investigated. B6.H-2(bm12) heart allografts induced low levels of alloreactive effector T cell priming in C57BL/6 recipients, and this priming was accompanied by low-level cellular infiltration into the allograft that quickly resolved. Recipients with long-term-surviving heart allografts were unable to reject B6.H-2(bm12) skin allografts, suggesting potential down-regulatory mechanisms induced by the cardiac allografts. Depletion of CD25(+) cells from C57BL/6 recipients resulted in 15-fold increases in alloreactive T cell priming and in acute rejection of B6.H-2(bm12) heart grafts. Similarly, reconstitution of B6.Rag(-/-) recipients with wild-type C57BL/6 splenocytes resulted in acute rejection of B6.H-2(bm12) heart grafts only if CD25(+) cells were depleted. These results indicate that acute rejection of single class II MHC-disparate B6.H-2(bm12) heart allografts by C57BL/6 recipients is inhibited by the emergence of CD25(+) regulatory cells that restrict the clonal expansion of alloreactive T cells.