Human allograft acceptance is associated with immune regulation
Human allograft acceptance is associated with immune regulation
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DOI：
10.1172/jci9171
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发表时间：
2000-07-01
影响因子：
15.9
通讯作者：
Orosz, CG
中科院分区：
文献类型：
--
作者：
VanBuskirk, AM;Burlingham, WJ;Orosz, CG
移植的最终目标是无药物的同种异体移植接受，这在移植受者中很少遇到。使用一种新的人-鼠“跨体”延迟型超敏试验，我们评估了肾和肝移植患者的供体反应性细胞介导的免疫反应，其中4例患者停止了所有免疫抑制。其中一名受试者（J.B.）在功能稳定7年后排斥了他的移植物，而其他受试者（d.s., r.d.， M.L.）在停止免疫抑制后的5年，28年和4年仍然具有良好的移植物功能。来自J.B.的PBMCs对供者抗原和回忆抗原都有强烈的反应，而来自d.s.、r.d.和M.L.的PBMCs对回忆抗原有强烈的反应，而对供者抗原没有反应。此外，当供体抗原和回忆抗原同时存在时，这三名患者的回忆反应被抑制。这种供体抗原相关的无反应性在另外四名仍然维持免疫抑制的患者中观察到。这些患者供体反应性甲状旁腺激素反应的薄弱是由于供体异体抗原触发的调节依赖于tgf - β或IL-10。在D.S中，调节是由单一供体HLA I类抗原触发的，要么是膜结合形式，要么是可溶性形式。这表明人类的同种异体移植接受与免疫调节模式有关，这可能对移植患者的同种异体移植接受的诊断和/或监测有用。
The ultimate goal of transplantation is drug-free allograft acceptance, which is rarely encountered in transplant recipients. Using a novel human-to-mouse "trans vivo" delayed-type hypersensitivity assay, we assessed donor-reactive cell-mediated immune responses in kidney and liver transplant patients, four of whom discontinued all immunosuppression. One of these subjects (J.B.) rejected his graft after 7 years of stable function, while the others (D.S., R.D., M.L.) continue to have excellent graft function 5, 28, and 4 years after the cessation of immunosuppression. PBMCs from J.B. exhibited strong responses to both donor and recall antigens whereas PBMCs from patients D.S., R.D., and M.L. responded strongly to recall, but not donor, antigens. Furthermore, when donor and recall antigens were colocalized, the recall response in these three patients was inhibited. This donor antigen-linked nonresponsiveness was observed in four other patients who are still maintained on immunosuppression. The weakness of donor-reactive DTH responses in these patients is due to donor alloantigen-triggered regulation that relies on either TGF-beta or IL-10. In D.S., regulation is triggered by a single donor HLA Class I antigen, either in membrane-bound or soluble form. This demonstrates that allograft acceptance in humans is associated with an immune regulation pattern, which may be useful in the diagnosis and/or monitoring of transplant patients for allograft acceptance.