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Role of ICOS pathway in autoimmune and alloimmune responses in NOD mice.

机译:ICOS途径在NOD小鼠自身免疫和同种免疫反应中的作用。

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Islet allografts are subject to alloimmune and autoimmune destruction when transplanted into autoimmune prone animals or humans. The ICOS-B7h pathway plays a role in alloimmune responses, but its function in autoimmunity against islet cells is controversial. We investigated the role of ICOS signaling in autoimmune and alloimmune responses in NOD mice. ICOS blockade prevents development of spontaneous disease in pre-diabetic NOD mice. Furthermore, while ICOS blockade prolongs graft survival in a fully mismatched non-autoimmune islet allograft model in C57BL/6 recipients, it has no beneficial effect in reversing diabetes in models of islet transplantation in NOD mice involving autoimmunity alone or both allo- and autoimmunity. Interestingly, ICOS blockade is effective in prolonging heart allograft (not subject to tissue-specific autoimmunity) survival in NOD mice. We conclude that in islet transplantation and autoimmune diabetes, ICOS blockade can be effective in inhibiting alloimmunity and preventing autoimmunity but is ineffective in inhibiting recurrence of autoimmunity.
机译:当将胰岛同种异体移植到易自身免疫的动物或人类体内时,会遭受同种免疫和自身免疫破坏。 ICOS-B7h途径在同​​种免疫反应中起作用,但其在针对胰岛细胞的自身免疫中的功能尚有争议。我们调查了ICOS信号传导在NOD小鼠自身免疫和同种免疫反应中的作用。 ICOS阻断可防止糖尿病前NOD小鼠自发性疾病的发展。此外,尽管在完全失配的非自体免疫胰岛同种异体移植模型中,ICOS阻断可延长C57BL / 6受者的移植物存活时间,但在单独涉及自身免疫或同体和自身免疫的NOD小鼠胰岛移植模型中,它对逆转糖尿病没有有益作用。有趣的是,ICOS阻断可有效延长NOD小鼠的心脏同种异体移植(不受组织特异性自身免疫)的存活。我们得出的结论是,在胰岛移植和自身免疫性糖尿病中,ICOS阻断可以有效抑制同种免疫和预防自身免疫,但不能有效抑制自身免疫的复发。

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