HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

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

AbstractBACKGROUND:
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.
AuthorsBenny J Chen, Yanfei Chen, Xiuyu Cui, John M Fidler, Nelson J Chao
JournalTransplantation (Transplantation) Vol. 73 Issue 1 Pg. 115-21 (Jan 15 2002) ISSN: 0041-1337 [Print] United States
PMID11792990 (Publication Type: Journal Article)
Chemical References
  • Cytokines
  • Diterpenes
  • Immunosuppressive Agents
  • omtriptolide
Topics
  • Animals
  • Animals, Newborn
  • Bone Marrow Transplantation (immunology)
  • CD4-Positive T-Lymphocytes (immunology)
  • CD8-Positive T-Lymphocytes (microbiology)
  • Cytokines (analysis)
  • Diterpenes (pharmacology)
  • Female
  • Graft Survival (drug effects, immunology)
  • Graft vs Host Disease (immunology, prevention & control)
  • Heart Transplantation (immunology)
  • Immunosuppression Therapy (methods)
  • Immunosuppressive Agents (pharmacology)
  • Lymph Nodes (immunology)
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred Strains
  • Models, Animal
  • Organ Size
  • Phytotherapy
  • T-Lymphocyte Subsets (immunology)
  • Time Factors
  • Transplantation, Homologous (immunology)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: