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. 2003 Dec 1;171(11):5673-7.
doi: 10.4049/jimmunol.171.11.5673.

V体育官网入口 - Cutting edge: transplantation tolerance through enhanced CTLA-4 expression

Charlotte Ariyan  1 , Paolo Salvalaggio, Scott Fecteau, Songyan Deng, Linda Rogozinski, Didier Mandelbrot, Arlene Sharpe, Mohamed H Sayegh, Giacomo P Basadonna, David M Rothstein
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Cutting edge: transplantation tolerance through enhanced CTLA-4 expression

Charlotte Ariyan et al. J Immunol. .

Abstract

Knockout and blocking studies have shown a critical role for CTLA-4 in peripheral tolerance, however, it is unknown whether augmenting CTLA-4 expression actually promotes tolerance. Here we demonstrate a specific and requisite role for CTLA-4 and its up-regulation in tolerance through anti-CD45RB. First, long-term murine islet allograft survival induced by anti-CD45RB is prevented by CTLA4-Ig, which interferes with B7:CTLA-4 interactions. Second, anti-CD45RB is ineffective in recipients lacking CTLA-4, B7-1, and B7-2. In contrast, CTLA4-Ig, which targets B7 on allogeneic cells, promotes long-term engraftment in these mice VSports手机版. Moreover, anti-CD45RB was effective in B7-deficient controls expressing CTLA-4. Finally, in wild-type mice, CTLA-4 expression returned to baseline 17 days after receiving anti-CD45RB, and was refractory to further increase. Transplantation and anti-CD45RB therapy at this time could neither augment CTLA-4 nor prolong engraftment. These data demonstrate a specific role for CTLA-4 in anti-CD45RB-mediated tolerance and indicate that CTLA-4 up-regulation can directly promote allograft survival. .

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