| First Author | Sheng-Tanner X | Year | 2000 |
| Journal | Transplantation | Volume | 70 |
| Issue | 12 | Pages | 1683-93 |
| PubMed ID | 11152097 | Mgi Jnum | J:66570 |
| Mgi Id | MGI:1928631 | Doi | 10.1097/00007890-200012270-00004 |
| Citation | Sheng-Tanner X, et al. (2000) Characterization of graft-versus-host disease in SCID mice and prevention by physicochemical stressors. Transplantation 70(12):1683-93 |
| abstractText | BACKGROUND: Graft versus host disease (GVHD) prevents potentially curative allogeneic stem cell transplantation from being offered to cancer patients who lack a suitably matched donor. New methods to prevent GVHD are required to allow successful transplants across major histocompatibility complex barriers. METHODS: A model of GVHD in C.B-17 SCID mice was developed to allow the study of allo-activated donor T cells without confounding effects of host lymphocytes. The abilities of cyclosporin-A, anticytokine antibodies, and oxidative stress to prevent GVHD in this model was studied. RESULTS: T cells from major histocompatibility-mismatched donor mice caused severe GVHD in sublethally irradiated SCID hosts that could be ameliorated by coadministration of donor bone marrow but not by cyclosporine-A or anticytokine antibodies. In contrast, three-log more T cells could be injected without clinical consequences if they had been pretreated with a combination of heat, ultraviolet light, and oxygenation. The effect was not the trivial result of donor T cell destruction because T cell reconstitution, although delayed, recovered to normal levels within 2 weeks. Protection from GVHD required oxygenation and was associated with normalization of the CD4/CD8 donor T cell ratio, recovery of host hematopoiesis, and decreased inflammatory cytokine production. CONCLUSION: Pretreatment of donor T cells with a combination of physicochemical stressors effectively prevents GVHD caused by major major histocompatibility disparities and may facilitate the safe transplantation of patients without HLA-identical donors. |
