Booster irradiation to the spleen following total body irradiation. A new immunosuppressive approach for allogeneic bone marrow transplantation
Journal Article
·
· J. Immunol.; (United States)
OSTI ID:6796899
Graft rejection presents a major obstacle for transplantation of T cell-depleted bone marrow in HLA-mismatched patients. In a primate model, after conditioning exactly as for leukemia patients, it was shown that over 99% of the residual host clonable T cells are concentrated in the spleen on day 5 after completion of cytoreduction. We have now corroborated these findings in a mouse model. After 9-Gy total body irradiation (TBI), the total number of Thy-1.2+ cells in the spleen reaches a peak between days 3 and 4 after TBI. The T cell population is composed of both L3T4 (helper) and Lyt-2 (suppressor) T cells, the former being the major subpopulation. Specific booster irradiation to the spleen (5 Gy twice) on days 2 and 4 after TBI greatly enhances production of donor-type chimera after transplantation of T cell-depleted allogeneic bone marrow. Similar enhancement can be achieved by splenectomy on day 3 or 4 after TBI but not if splenectomy is performed 1 day before TBI or 1 day after TBI, strengthening the hypothesis that, after lethal TBI in mice, the remaining host T cells migrate from the periphery to the spleen. These results suggest that a delayed booster irradiation to the spleen may be beneficial as an additional immunosuppressive agent in the conditioning of leukemia patients, in order to reduce the incidence of bone marrow allograft rejection.
- Research Organization:
- Weizmann Institute of Science, Rehovot (Israel)
- OSTI ID:
- 6796899
- Journal Information:
- J. Immunol.; (United States), Journal Name: J. Immunol.; (United States) Vol. 141:8; ISSN JOIMA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
560152* -- Radiation Effects on Animals-- Animals
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMAL TISSUES
ANIMALS
BIOLOGICAL MATERIALS
BIOLOGICAL MODELS
BLOOD
BLOOD CELLS
BODY
BODY FLUIDS
BONE MARROW
CHIMERAS
CONNECTIVE TISSUE CELLS
DISEASES
EXTERNAL IRRADIATION
GRAFT-HOST REACTION
HEMATOPOIETIC SYSTEM
HEMIC DISEASES
IMMUNE SYSTEM DISEASES
IMMUNITY
IMMUNOSUPPRESSION
IRRADIATION
LEUKEMIA
LEUKOCYTES
LYMPHOCYTES
MAMMALS
MATERIALS
MEDICINE
MICE
MOSAICISM
NEOPLASMS
ORGANS
RADIATION CHIMERAS
RADIOINDUCTION
RODENTS
SOMATIC CELLS
SPLEEN
SPLENECTOMY
SURGERY
TISSUES
TRANSPLANTS
VERTEBRATES
WHOLE-BODY IRRADIATION
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMAL TISSUES
ANIMALS
BIOLOGICAL MATERIALS
BIOLOGICAL MODELS
BLOOD
BLOOD CELLS
BODY
BODY FLUIDS
BONE MARROW
CHIMERAS
CONNECTIVE TISSUE CELLS
DISEASES
EXTERNAL IRRADIATION
GRAFT-HOST REACTION
HEMATOPOIETIC SYSTEM
HEMIC DISEASES
IMMUNE SYSTEM DISEASES
IMMUNITY
IMMUNOSUPPRESSION
IRRADIATION
LEUKEMIA
LEUKOCYTES
LYMPHOCYTES
MAMMALS
MATERIALS
MEDICINE
MICE
MOSAICISM
NEOPLASMS
ORGANS
RADIATION CHIMERAS
RADIOINDUCTION
RODENTS
SOMATIC CELLS
SPLEEN
SPLENECTOMY
SURGERY
TISSUES
TRANSPLANTS
VERTEBRATES
WHOLE-BODY IRRADIATION