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Title: 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

Abstract

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 withmore » 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.« less

Authors:
; ; ; ; ;  [1]
  1. National Cancer Institute, Bethesda, MD (USA)
Publication Date:
OSTI Identifier:
5044535
Resource Type:
Journal Article
Journal Name:
Journal of Immunology; (USA)
Additional Journal Information:
Journal Volume: 143:11; Journal ID: ISSN 0022-1767
Country of Publication:
United States
Language:
English
Subject:
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.; 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

Citation Formats

Sykes, M, Chester, C H, Sundt, T M, Romick, M L, Hoyles, K A, and Sachs, D H. 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. United States: N. p., 1989. Web.
Sykes, M, Chester, C H, Sundt, T M, Romick, M L, Hoyles, K A, & Sachs, D H. 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. United States.
Sykes, M, Chester, C H, Sundt, T M, Romick, M L, Hoyles, K A, and Sachs, D H. 1989. "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". United States.
@article{osti_5044535,
title = {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},
author = {Sykes, M and Chester, C H and Sundt, T M and Romick, M L and Hoyles, K A and Sachs, D H},
abstractNote = {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.},
doi = {},
url = {https://www.osti.gov/biblio/5044535}, journal = {Journal of Immunology; (USA)},
issn = {0022-1767},
number = ,
volume = 143:11,
place = {United States},
year = {Fri Dec 01 00:00:00 EST 1989},
month = {Fri Dec 01 00:00:00 EST 1989}
}