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Graft-versus-host disease prevention by rapamycin: cellular mechanisms.

Publication ,  Journal Article
Chen, BJ; Morris, RE; Chao, NJ
Published in: Biol Blood Marrow Transplant
2000

Understanding the cellular mechanisms that lead to graft-versus-host disease (GVHD) may lead to alternative approaches in the prevention or therapy of this disease process. In this manuscript, we investigated the mechanisms of action of the immunosuppressive drug rapamycin for the prevention of GVHD. GVHD-free long-term survival was achieved in BALB/c (H2d, Mls-2a, Mls-3a) recipients of B10.D2/nSnJ (H-2d, Mls-2a, Mls-3a) bone marrow and spleen cells after a 30-day course of high-dose rapamycin (5 mg/kg per day). Low responses to recipient and third-party cells in a mixed lymphocyte reaction (MLR) were observed as well as decreased mature T-cell numbers in the spleen. This low response was not due to defective interleukin (IL)-2 production, because exogenous IL-2 did not improve the responses in the MLR. However, GVHD-free long-term survival was associated with a large number of infiltrating mononuclear cells in the target organs of GVHD. This observation suggested the possibility that these cells were responsible for suppressing the immune response. Regulatory cells, which could suppress both antirecipient and third-party responses in vitro, were demonstrated to be present in the spleens of these GVHD-free long-term survivors. These results suggest that in addition to impaired cellular immune function, the presence of non-specific regulatory cells (ie, suppression) may contribute to maintenance of GVHD-free long-term survival induced by short-course rapamycin.

Duke Scholars

Published In

Biol Blood Marrow Transplant

DOI

ISSN

1083-8791

Publication Date

2000

Volume

6

Issue

5A

Start / End Page

529 / 536

Location

United States

Related Subject Headings

  • Transplantation, Homologous
  • T-Lymphocytes, Cytotoxic
  • Spleen
  • Specific Pathogen-Free Organisms
  • Skin
  • Sirolimus
  • Radiation Chimera
  • Minor Lymphocyte Stimulatory Antigens
  • Mice, Inbred C57BL
  • Mice, Inbred BALB C
 

Citation

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ICMJE
MLA
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Chen, B. J., Morris, R. E., & Chao, N. J. (2000). Graft-versus-host disease prevention by rapamycin: cellular mechanisms. Biol Blood Marrow Transplant, 6(5A), 529–536. https://doi.org/10.1016/s1083-8791(00)70062-0
Chen, B. J., R. E. Morris, and N. J. Chao. “Graft-versus-host disease prevention by rapamycin: cellular mechanisms.Biol Blood Marrow Transplant 6, no. 5A (2000): 529–36. https://doi.org/10.1016/s1083-8791(00)70062-0.
Chen BJ, Morris RE, Chao NJ. Graft-versus-host disease prevention by rapamycin: cellular mechanisms. Biol Blood Marrow Transplant. 2000;6(5A):529–36.
Chen, B. J., et al. “Graft-versus-host disease prevention by rapamycin: cellular mechanisms.Biol Blood Marrow Transplant, vol. 6, no. 5A, 2000, pp. 529–36. Pubmed, doi:10.1016/s1083-8791(00)70062-0.
Chen BJ, Morris RE, Chao NJ. Graft-versus-host disease prevention by rapamycin: cellular mechanisms. Biol Blood Marrow Transplant. 2000;6(5A):529–536.
Journal cover image

Published In

Biol Blood Marrow Transplant

DOI

ISSN

1083-8791

Publication Date

2000

Volume

6

Issue

5A

Start / End Page

529 / 536

Location

United States

Related Subject Headings

  • Transplantation, Homologous
  • T-Lymphocytes, Cytotoxic
  • Spleen
  • Specific Pathogen-Free Organisms
  • Skin
  • Sirolimus
  • Radiation Chimera
  • Minor Lymphocyte Stimulatory Antigens
  • Mice, Inbred C57BL
  • Mice, Inbred BALB C