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- Title
CD40Ig treatment results in allograft acceptance mediated by CD8+CD45RClow T cells, IFN-, and indoleamine 2,3-dioxygenase.
- Authors
Guillonneau, Carole; Hill, Marcelo; Hubert, François-Xavier; Chiffoleau, Elise; Hervé, Caroline; Xian-Liang Li; Heslan, Michèle; Usal, Claire; Tesson, Laurent; Ménoret, Séverine; Saoudi, Abdelhadi; Le Mauff, Brigitte; Josien, Régis; Cuturi, Maria Cristina; Anegon, Ignacio
- Abstract
Treatment with CD40Ig results in indefinite allograft survival in a complete MHC-mismatched heart allograft model in the rat. Here we show that serial second, third, and fourth adoptive transfers of total splenocytes from CD40Ig-treated recipients into secondary recipients led to indefinite donor-specific allograft acceptance. Purification of splenocyte subpopulations from CD40Ig-treated recipients demonstrated that only the adoptively transferred CD8+CD45RClow subset resulted in donor-specific long-term survival, whereas CD8+CD45RClow T cells from naive animals did not. Accepted grafts displayed increased indoleamine 2,3-dioxygenase (IDO) expression restricted in the graft to ECs. Coculture of donor ECs with CD8+CD45RClow T cells purified from CD40Ig-treated animals resulted in donor-specific IDO expression dependent on IFN-. Neutralization of IFN- or IDO triggered acute allograft rejection in both CD40Ig-treated and adoptively transferred recipients. This study demonstrates for what we believe to be the first time that interference in CD40CD40 ligand (CD40-CD40L) interactions induces allospecific CD8+ Tregs that maintain allograft survival. CD8+CD45RClow T cells act through IFN- production, which in turn induces IDO expression by graft ECs. Thus, donor alloantigen-specific CD8+ Tregs may promote local graft immune privilege through IDO expression.
- Subjects
HOMOGRAFTS; LYMPHOCYTES; TRANSPLANTATION of organs, tissues, etc.; HEART transplantation; CELL-mediated lympholysis; T cells
- Publication
Journal of Clinical Investigation, 2007, Vol 117, Issue 4, p1096
- ISSN
0021-9738
- Publication type
Article
- DOI
10.1172/JCI28801