Early T cell response to allografts occuring prior to alloantigen priming up-regulates innate-mediated inflammation and graft necrosis
Early T cell response to allografts occuring prior to alloantigen priming up-regulates innate-mediated inflammation and graft necrosis
复制标题
DOI：
10.1016/s0002-9440(10)63283-x
复制
发表时间：
2004-07-01
影响因子：
6
通讯作者：
Fairchild, R
中科院分区：
文献类型：
--
作者：
El-Sawy, T;Miura, M;Fairchild, R
同种异体器官移植的早期炎症反应是由缺血/再灌注（I/R）引发的，并促进随后的同种异体抗原启动的T细胞募集进入移植物和排斥反应。多形核白细胞（PMN）介导的组织损伤是同种异体移植排斥反应早期炎症的主要组成部分。我们试图比较和阐明PMN早期浸润到心脏同种异体移植物和同种异体移植物中的机制。尽管产生相同的PMN引诱趋化因子，但同体和异体移植物再灌注后的PMN浸润并不相等。PMN在移植后9 ~ 12小时达到浸润高峰，并迅速消退。相比之下，同种异体移植物的PMN浸润继续升高，在再灌注后24小时达到峰值。再灌注后72小时，同种异体移植物内的PMN浸润才消失，并伴有明显的实质坏死。在可检测到的同种异体抗原T细胞启动之前，受体中存在ifn - γ产生CD8(+) T细胞，这种早期先天炎症反应受到ifn - γ产生CD8(+) T细胞的调节。与CD62L（低）CD8(+) T细胞共培养，但不与CD62L（高）CD8（+）或CD62L（低）CD4(+) T细胞共培养，从幼稚动物诱导异体内皮细胞表达ifn - γ依赖性趋化因子。这些数据表明，在器官再灌注后数小时内，CD8(+) T细胞介导的对同种异体移植物血管内皮的攻击放大了先天免疫介导的移植物内炎症和坏死。
The early inflammatory response within organ allografts is initiated by ischemia/reperfusion (I/R) and promotes subsequent alloantigen-primed T cell recruitment into and rejection of the graft. Polymorphonuclear leukocyte (PMN)-mediated tissue damage is a primary component of the early inflammation in allograft rejection. We sought to compare and elucidate the mechanism of early PMN infiltration into cardiac isografts and allografts. Despite identical production of PMN attractant chemokines, PMN infiltration following reperfusion into syngeneic and allogeneic grafts was not equivalent. PMN infiltration into isografts peaked at 9 to 12 hours post-transplant and quickly resolved. In contrast, PMN infiltration into allografts continued to elevated levels, peaking at 24 hours post-reperfusion. This amplified PMN infiltration into allografts did not resolve until 72 hours post-reperfusion and was accompanied by marked parenchymal necrosis. This early innate inflammatory response was regulated by IFN-gamma-producing CD8(+) T cells present in the recipient before detectable alloantigen T cell priming. Co-culture with CD62L(low)CD8(+) T cells, but not CD62L(high) CD8(+) or CD62L(low) CD4(+) T cells, harvested from naive animals induced allogeneic endothelial cells to express IFN-gamma-dependent chemokines. These data demonstrate CD8(+) T cell-mediated attack on the vascular endothelium of allografts within hours following organ reperfusion that amplifies innate immune-mediated intra-graft inflammation and necrosis.