| First Author | Iwasaki T | Year | 2000 |
| Journal | Immunology | Volume | 99 |
| Issue | 1 | Pages | 94-100 |
| PubMed ID | 10651946 | Mgi Jnum | J:59406 |
| Mgi Id | MGI:1351545 | Doi | 10.1046/j.1365-2567.2000.00919.x |
| Citation | Iwasaki T, et al. (2000) Graft-versus-host-disease-associated donor cell engraftment in an F1 hybrid model is dependent upon the Fas pathway. Immunology 99(1):94-100 |
| abstractText | The graft-versus-host disease (GVHD) generated in BDF1 mice by the injection of spleen cells from the C57BL/6 parental strain induces a direct cell-mediated attack on host lymphohaematopoietic populations, resulting in the reconstitution of the host with donor cells. We examined Fas-Fas ligand (FasL) interactions in donor and host haematopoietic cells over a prolonged period of parental-induced GVHD. Fas expression on bone marrow cells of both donor and host origin increased at 2 weeks. Host cell incubation with anti-Fas antibody induced apoptosis, and the number of haematopoietic progenitor cells decreased. Fas-induced apoptosis by the repopulating donor cells, however, did not increase until 12 weeks, when more than 90% of the cells were donor cells. The expression of various cytokines, such as interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha), and FasL gene expression in the bone marrow increased concomitantly. To examine directly whether FasL has a major role in the development of donor cell engraftment, FasL-deficient (gld) mice were used as donors. Injection of B6/gld spleen cells induced significantly less host lymphohaematopoietic depletion, resulting in a failure of donor cell engraftment. Furthermore, injection of IFN-gamma gene knockout (gko) B6 spleen cells failed to augment Fas and FasL expression in recipient mice, resulting in a failure of donor cell engraftment. This suggests that the induction of apoptosis by Fas-FasL interactions in host cells may contribute to a reconstitution of the host with donor cells and that donor-derived IFN-gamma plays a significant role for Fas-FasL interactions in host cells during parental-induced GVHD. |
