Effects of T cell depletion in radiation bone marrow chimeras. III. Characterization of allogeneic bone marrow cell populations that increase allogeneic chimerism independently of graft-vs-host disease in mixed marrow recipients
- National Cancer Institute, Bethesda, MD (USA)
The opposing problems of graft-vs-host disease vs failure of alloengraftment severely limit the success of allogeneic bone marrow transplantation as a therapeutic modality. We have recently used a murine bone marrow transplantation model involving reconstitution of lethally irradiated mice with mixtures of allogeneic and syngeneic marrow to demonstrate that an allogeneic bone marrow subpopulation, removed by T cell depletion with rabbit anti-mouse brain serum and complement (RAMB/C), is capable of increasing levels of allogeneic chimerism. This effect was observed in an F1 into parent genetic combination lacking the potential for graft-vs-host disease, and radiation protection studies suggested that it was not due to depletion of stem cells by RAMB/C. We have now attempted to characterize the cell population responsible for increasing allogeneic chimerism in this model. The results indicate that neither mature T cells nor NK cells are responsible for this activity. However, an assay involving mixed marrow reconstitution in an Ly-5 congenic strain combination was found to be more sensitive to small degrees of stem cell depletion than radiation protection assays using three-fold titrations of bone marrow cells. Using this assay, we were able to detect some degree of stem cell depletion by treatment with RAMB/C, but not with anti-T cell mAb. Nevertheless, if the effects of alloresistance observed in this model are considered, the degree of stem cell depletion detected by such mixing studies in insufficient to account for the effects of RAMB/C depletion on levels of allogeneic chimerism, suggesting that another cell population with this property remains to be identified.
- OSTI ID:
- 5044535
- Journal Information:
- Journal of Immunology; (USA), Vol. 143:11; ISSN 0022-1767
- Country of Publication:
- United States
- Language:
- English
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BONE MARROW
TRANSPLANTS
LYMPHOCYTES
BIOLOGICAL FUNCTIONS
STEM CELLS
INHIBITION
BIOASSAY
BIOLOGICAL MODELS
COMPLEMENT
GRAFT-HOST REACTION
MICE
MONOCLONAL ANTIBODIES
RADIATION CHIMERAS
RADIATION PROTECTION
RATS
ANIMAL CELLS
ANIMAL TISSUES
ANIMALS
ANTIBODIES
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY
BODY FLUIDS
CHIMERAS
CONNECTIVE TISSUE CELLS
FUNCTIONS
HEMATOPOIETIC SYSTEM
LEUKOCYTES
MAMMALS
MATERIALS
MOSAICISM
ORGANIC COMPOUNDS
ORGANS
PROTEINS
RODENTS
SOMATIC CELLS
TISSUES
VERTEBRATES
560152* - Radiation Effects on Animals- Animals