Open AccessFasL IS IMPORTANT IN COSTIMULATION BLOCKADE-RESISTANT SKIN GRAFT REJECTION
Author(s) -
Joel Trambley,
Angello Lin,
Eric T. Elwood,
Adam W. Bingaman,
Fadi G. Lakkis,
Matthias Corbascio,
Thomas C. Pearson,
Christian Larsen
Publication year - 2001
Publication title -
transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.45
H-Index - 204
eISSN - 1534-6080
pISSN - 0041-1337
DOI - 10.1097/00007890-200102270-00009
Subject(s) - blockade , fas ligand , immunology , cd28 , cd8 , medicine , apoptosis , immune system , biology , cancer research , receptor , programmed cell death , biochemistry
Simultaneous blockade of the CD40 and CD28 costimulatory pathways is effective in prolonging allograft survival in murine and primate models. Recent data suggest that intact apoptotic pathways are crucial for the induction of hyporesponsiveness by costimulation blockade. We have studied the impact of fas/fasL signaling, an important T cell apoptotic pathway, on the effects of costimulation blockade. Methods. Wild type, lpr (fas deficient), and gld (fasL deficient), mice were used as donors and recipients in the murine skin graft model. Allograft survival was compared in untreated and costimulation blockade (500 microg anti-CD40L and 500 microg CTLA4-Ig, days 0, 2, 4, 6) treated recipients. In some recipients, CD4+ T cells were depleted using rat anti-murine CD4 (100 microg day -3, -2, -1, and weekly).