Zhao Y, Fishman J A, Sergio J J, Oliveros J L, Pearson D A, Szot G L, Wilkinson R A, Arn J S, Sachs D H, Sykes M
Transplantation Biology Research Center, Massachusetts General Hospital/Harvard Medical School, Boston 02129, USA.
J Immunol. 1997 Feb 15;158(4):1641-9.
Donor-specific tolerance can be induced across a discordant xenogeneic barrier in T/NK cell-depleted, thymectomized (ATX) B10 mice by grafting of fetal pig thymic and liver tissue (FP THY/LIV) under the kidney capsule. We have now examined the phenotype and function of murine T cells that develop in FP THY/LIV grafts in these mice. Mouse CD4+ T cells reached normal levels in PBL by 14 wk, and were maintained up to 30 wk. Similar proportions of splenic CD4+ cells expressed the naive phenotype (CD45RBhighMEL-14+CD44low) in FP THY/LIV graft recipients and euthymic control mice. These CD4 cells were functional, demonstrating normal proliferative responses and up-regulation of CD25 and CD69 after activation by mitogens or alloantigens. They proliferated in response to the protein Ag KLH presented by host MHC following in vivo immunization. ATX B10 mice grafted with FP THY/LIV also cleared Pneumocystis carinii infections, whereas simultaneously-treated ATX B10 mice not receiving FP THY were unable to do so. Discordant xenogeneic thymus grafting can therefore restore immune competence. Thus, in addition to tolerance induction, xenogeneic thymic replacement might have a potential role in the reconstitution of immunity in patients afflicted with immunodeficiencies affecting the thymus.
通过在肾被膜下移植胎猪胸腺和肝脏组织（FP THY/LIV），可在T/NK细胞缺失、胸腺切除（ATX）的B10小鼠中跨越不匹配的异种屏障诱导供体特异性耐受。我们现在研究了在这些小鼠的FP THY/LIV移植物中发育的鼠T细胞的表型和功能。小鼠CD4⁺ T细胞在14周时外周血淋巴细胞（PBL）中达到正常水平，并维持到30周。在接受FP THY/LIV移植物的小鼠和正常胸腺的对照小鼠中，脾CD4⁺细胞表达幼稚表型（CD45RB高MEL-14⁺CD44低）的比例相似。这些CD4细胞具有功能，在被丝裂原或同种异体抗原激活后表现出正常的增殖反应以及CD25和CD69的上调。在体内免疫后，它们对宿主MHC呈递的蛋白质抗原钥孔戚血蓝蛋白（KLH）发生增殖反应。移植了FP THY/LIV的ATX B10小鼠也清除了卡氏肺孢子虫感染，而同时处理但未接受FP THY的ATX B10小鼠则无法清除。因此，不匹配的异种胸腺移植可以恢复免疫能力。因此，除了诱导耐受外，异种胸腺替代可能在免疫缺陷影响胸腺的患者的免疫重建中具有潜在作用。
