Faculty Research 1990 - 1999
An essential role for Fas ligand in transplantation tolerance induced by donor bone marrow.
Document Type
Article
Publication Date
1998
First Page
333
Last Page
335
JAX Source
Nat Med 1998 Mar;4(3):333-5
Abstract
Medawar and co-workers originally demonstrated that injection of donor bone marrow (DBM) into immuno-incompetent neonatal rodents could induce tolerance to grafts from animals of the same strain as the bone marrow donor. Induction of tolerance in this manner can also be accomplished in mature mice, dogs and monkeys if the resident T-cell populations in the recipient are depleted by a polyclonal antithymocyte globulin or an anti-T cell immunotoxin. The molecular mechanisms by which bone marrow cells mediate the induction of tolerance remain uncertain. Here we examined a well-established adult mouse model of antithymocyte globulin and DBM treatment and show that expression of functional Fas ligand (FasL, also CD95L) on the injected bone marrow cells is required for tolerance induction. The results indicate that a state of microchimerism per se is insufficient for the induction of tolerance in T cell-depleted transplant recipients. Moreover, the results are consistent with the hypothesis that tolerance induced by DBM involves an apoptotic process leading to deletion of graft-reactive cells.
Recommended Citation
George JF,
Sweeney SD,
Kirklin JK,
Simpson EM,
Goldstein DR,
Thomas JM.
An essential role for Fas ligand in transplantation tolerance induced by donor bone marrow. Nat Med 1998 Mar;4(3):333-5