Elwood E T, Larsen C P, Cho H R, Corbascio M, Ritchie S C, Alexander D Z, Tucker-Burden C, Linsley P S, Aruffo A, Hollenbaugh D, Winn K J, Pearson T C
Department of Surgery, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Transplantation. 1998 Jun 15;65(11):1422-8. doi: 10.1097/00007890-199806150-00002.
The prompt and vigorous immune response to xenogenic tissue remains a significant barrier to clinical xenotransplantation. Simultaneous blockade of the CD28 and CD40 costimulatory pathways has been shown to dramatically inhibit the immune response to alloantigen.
. In this study, we investigated the ability of simultaneous blockade of the CD28 and CD40 pathways to inhibit the immune response to xenoantigen in the rat-to-mouse and pig-to-mouse models.
Simultaneous blockade of the CD28 and CD40 pathways produced marked inhibition of the cellular response to xenoantigen in vivo and produced long-term acceptance of xenogeneic cardiac and skin grafts (rat-to-mouse), and markedly suppressed an evoked antibody response to xenoantigen. In addition, this strategy significantly prolonged the survival of pig skin on recipient mice.
Long-term hyporesponsiveness to xenoantigen across both a concordant and discordant species barrier, measured by the stringent criterion of skin grafting, can be achieved using a noncytoablative treatment regimen.
对异种组织迅速而强烈的免疫反应仍然是临床异种移植的重大障碍。已证明同时阻断CD28和CD40共刺激途径可显著抑制对同种异体抗原的免疫反应。
在本研究中，我们研究了同时阻断CD28和CD40途径在大鼠到小鼠和猪到小鼠模型中抑制对异种抗原免疫反应的能力。
同时阻断CD28和CD40途径在体内对异种抗原的细胞反应产生了显著抑制，并使异种心脏和皮肤移植物（大鼠到小鼠）获得长期接受，且显著抑制了对异种抗原诱发的抗体反应。此外，该策略显著延长了猪皮肤在受体小鼠上的存活时间。
通过严格的皮肤移植标准衡量，使用非清髓性治疗方案可实现跨越协调和不协调物种屏障对异种抗原的长期低反应性。
