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Mechanisms of tolerance induced by PG490-88 in a bone marrow transplantation model.

Publication ,  Journal Article
Chen, BJ; Chen, Y; Cui, X; Fidler, JM; Chao, NJ
Published in: Transplantation
January 15, 2002

BACKGROUND: PG490-88, a semisynthetic derivative of a novel compound PG490 (triptolide) purified from a Chinese herb (Tripterygium wilfordii Hook F), is effective in prevention of murine graft-versus-host disease (GVHD). METHODS: PG490-88 was administrated into recipients in a model (B10.D2 [H2d, Mls-2b, Mls-3b]-->BALB/c [H2d, Mls-2a, Mls-3a]) of lethal GVHD. Tolerance was evaluated by transplantation of neonatal hearts. The mechanisms of tolerance were studied. RESULTS: Host-specific tolerance was established in PG490-88-treated BALB/c recipients. Significant numbers of host reactive Vbeta3+ T cells (3.56+/-1.66% among CD4, 4.06+/-1.62% among CD8, P<0.0001 vs. normal BALB/c mice, P>0.05 vs. normal B10.D2 mice) were present in PG490-88-treated mice, suggesting that clonal deletion was not responsible for the observed tolerance. Spleen cells from PG490-88-treated mice could not respond to the host antigens measured by a popliteal lymph node weight gain assay. The unresponsiveness was unable to be overcome by supplementation of exogenous interleukin (IL)-2. Tolerant Vbeta3+ T cells obtained from PG490-88-treated mice proliferated normally to nonantigen-specific T cell receptor cross-linking. Neither antigen-specific nor nonantigen-specific suppressor cells were found in PG490-88-treated mice. The tolerant mice produced IL-4 rather than IL-2 and interferon (IFN)-gamma. CONCLUSIONS: Host-specific tolerance induced by PG490-88 in a murine bone marrow transplantation model is not due to deletion of alloreactive cells. Moreover, suppressor cells are not involved in the maintenance of tolerance. Rather, PG490-88 seems to lead to allogeneic tolerance either through the induction of a state of antigen-specific anergy of the responding T cells or through the induction of T-helper cell, type II (TH2) responses.

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Published In

Transplantation

DOI

ISSN

0041-1337

Publication Date

January 15, 2002

Volume

73

Issue

1

Start / End Page

115 / 121

Location

United States

Related Subject Headings

  • Transplantation, Homologous
  • Time Factors
  • T-Lymphocyte Subsets
  • Surgery
  • Phytotherapy
  • Organ Size
  • Models, Animal
  • Mice, Inbred Strains
  • Mice, Inbred BALB C
  • Mice
 

Citation

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Chen, B. J., Chen, Y., Cui, X., Fidler, J. M., & Chao, N. J. (2002). Mechanisms of tolerance induced by PG490-88 in a bone marrow transplantation model. Transplantation, 73(1), 115–121. https://doi.org/10.1097/00007890-200201150-00022
Chen, Benny J., Yanfei Chen, Xiuyu Cui, John M. Fidler, and Nelson J. Chao. “Mechanisms of tolerance induced by PG490-88 in a bone marrow transplantation model.Transplantation 73, no. 1 (January 15, 2002): 115–21. https://doi.org/10.1097/00007890-200201150-00022.
Chen BJ, Chen Y, Cui X, Fidler JM, Chao NJ. Mechanisms of tolerance induced by PG490-88 in a bone marrow transplantation model. Transplantation. 2002 Jan 15;73(1):115–21.
Chen, Benny J., et al. “Mechanisms of tolerance induced by PG490-88 in a bone marrow transplantation model.Transplantation, vol. 73, no. 1, Jan. 2002, pp. 115–21. Pubmed, doi:10.1097/00007890-200201150-00022.
Chen BJ, Chen Y, Cui X, Fidler JM, Chao NJ. Mechanisms of tolerance induced by PG490-88 in a bone marrow transplantation model. Transplantation. 2002 Jan 15;73(1):115–121.

Published In

Transplantation

DOI

ISSN

0041-1337

Publication Date

January 15, 2002

Volume

73

Issue

1

Start / End Page

115 / 121

Location

United States

Related Subject Headings

  • Transplantation, Homologous
  • Time Factors
  • T-Lymphocyte Subsets
  • Surgery
  • Phytotherapy
  • Organ Size
  • Models, Animal
  • Mice, Inbred Strains
  • Mice, Inbred BALB C
  • Mice