Cutting edge: transplantation tolerance through enhanced CTLA-4 expression. Academic Article uri icon

Overview

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. 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.

authors

  • Ariyan, Charlotte
  • Salvalaggio, Paolo
  • Fecteau, Scott
  • Deng, Songyan
  • Rogozinski, Linda
  • Mandelbrot, Didier
  • Sharpe, Arlene
  • Sayegh, Mohamed H
  • Basadonna, Giacomo P
  • Rothstein, David M

publication date

  • December 1, 2003

Research

keywords

  • Adjuvants, Immunologic
  • Antigens, Differentiation
  • Graft Enhancement, Immunologic
  • Transplantation Tolerance

Identity

Scopus Document Identifier

  • 10744226680

Digital Object Identifier (DOI)

  • 10.4049/jimmunol.171.11.5673

PubMed ID

  • 14634073

Additional Document Info

volume

  • 171

issue

  • 11