Abstract | BACKGROUND: 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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Authors | Benny J Chen, Yanfei Chen, Xiuyu Cui, John M Fidler, Nelson J Chao |
Journal | Transplantation
(Transplantation)
Vol. 73
Issue 1
Pg. 115-21
(Jan 15 2002)
ISSN: 0041-1337 [Print] United States |
PMID | 11792990
(Publication Type: Journal Article)
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Chemical References |
- Cytokines
- Diterpenes
- Immunosuppressive Agents
- omtriptolide
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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)
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