title: Characterization of graft-versus-host disease in SCID mice and prevention by physicochemical stressors.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Cancer Biology Research, Sunnybrook and Women's College Health Sciences Centre, Toronto, Ontario, Canada.
authors.forename: X
authors.initials: X
authors.lastname: Sheng-Tanner
authors.forename: C
authors.initials: C
authors.lastname: McKerlie
authors.forename: D
authors.initials: D
authors.lastname: Spaner
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000276:immunology; D016572:Cyclosporine / Q000494:pharmacology; D016207:Cytokines / Q000276:immunology; D004195:Disease Models, Animal; D006086:Graft vs Host Disease / Q000209:etiology* / Q000276:immunology / Q000517:prevention & control*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008285:Major Histocompatibility Complex; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D018384:Oxidative Stress; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000637:transplantation; D014019:Tissue Donors; D014184:Transplantation, Homologous
chemical_list: D000906:Antibodies; D016207:Cytokines; D007166:Immunosuppressive Agents; D016572:Cyclosporine