Lethal graft-versus-host disease in nude mice. I. Establishment of model systems
We examined whether nude mice, which are deficient in T cell function, could be used as a model for induction of lethal graft-versus-host disease. Nude mice injected with MHC-disparate spleen cells exhibited only transient GVH reaction such as splenomegaly. Inoculation of B6 spleen cells into BALB/c nude mice produced high titers of alloantibodies to the donor cells. These alloantibodies eliminated host-MHC-reactive donor T cells from the host. After abolition by 400 rads irradiation of the capacity of nude mice to produce antibody, lethal GVHD could be induced by allogeneic spleen cell transfer and was mediated by donor T cells. This lethal GVHD was prevented by prior administration of antidonor alloantibody to the irradiated recipients at least 24 hr before donor-cell grafting. The role of alloantibody was substantiated in 2 other combinations in which little or no alloantibodies to donor spleen cells were produced. Engraftment of either MHC-identical but non-MHC disparate donor spleen cells into BALB/c nude mice or of parental spleen cells into F1 nude mice resulted in death mediated by T cells. In addition, irradiated BALB/c nude mice inoculated with non-MHC-incompatible B10.D2 spleen cells were much more sensitive to alloaggression by the donor cells than were nonirradiated hosts, indicating the presence of some radiation-sensitive component(s) acting in nude mice against GVHD induction by donor T cells. Thus the nude mouse is considered to be a useful recipient for clarifying the basic mechanisms involved in lethal GVHD.
- Research Organization:
- Institute for Immunology, Kyoto (Japan)
- OSTI ID:
- 6861859
- Journal Information:
- Transplantation; (United States), Vol. 46:2
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
GRAFT-HOST REACTION
BIOLOGICAL MODELS
IMMUNITY
RADIOINDUCTION
ANTIBODY FORMATION
LYMPHOCYTES
MICE
SPLEEN CELLS
ANIMAL CELLS
ANIMALS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CONNECTIVE TISSUE CELLS
LEUKOCYTES
MAMMALS
MATERIALS
RODENTS
SOMATIC CELLS
VERTEBRATES
560152* - Radiation Effects on Animals- Animals