J Immunol. 1996 Dec 15;157(12):5387-93.

A major role for the Fas pathway in acute graft-versus-host disease.

Via CS, Nguyen P, Shustov A, Drappa J, Elkon KB.

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Research Service, Department of Veteran Affairs Medical Center, and Division of Rheumatology and Clinical Immunology, University of Maryland School of Medicine, Baltimore 21201, USA.

Abstract

Recent studies have suggested a role for the Fas pathway in the wasting syndrome associated with lpr-->wild-type bone marrow transplants. To directly examine whether Fas ligand has a major role in the development of acute graft-vs-host disease (GVHD), Fas ligand-deficient (gld) mice were used as donors and C3H/HeJ x C57BL/6F1 as recipients in the parent-into-F1 model of acute GVHD. Transplantation of C3H/gld spleen cells induced significantly less host lymphoid depletion and was associated with less antihost cytotoxic activity in vitro when compared with wild-type C3H donor cells. The reduced depletion of host lymphocytes was explained by both impaired antihost T cell cytolytic activity and by reduced expansion of gld donor T cells in F1 recipients. These findings not only indicate that the Fas ligand is an important effector molecule in acute GVHD, but also provide in vivo evidence supporting a role for Fas/Fas ligand interactions in T cell expansion and maturation.

PMID:: 8955186; [PubMed - indexed for MEDLINE]

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