Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.1.1.148 (Thy1)
 1,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To examine the influence of FK506 on lymphocyte development, we employed a syngeneic bone marrow transplantation model using MHC-disparate B10 (H-2b, I-Ab) and B10.BR (H-2k, I-Ak, I-Ek) mice. B10 mice, which do not express class II I-E, do not delete any known T cell receptor (TCR)-V beta, while B10.BR mice (MHC class II I-Ek, I-Ak) delete V beta 5+ and V beta 11+ TCR. Continuous daily treatment of syngeneically reconstituted B10 mice with FK506 delayed the development of thymocytes from the CD4+CD8+ to CD4+CD8- stage, while no effect was observed at the earlier CD4-CD8- to CD4+CD8+ stage. At the same time, there was a significant reduction in TCRhigh thymocytes compared with untreated, syngeneically reconstituted controls. These results suggest that FK506 treatment interfered with thymic positive selection. We also examined whether FK506 treatment would influence negative selection. Levels of expression of V beta 5+ and V beta 11+ T cells in FK506-treated B10.BR-->B10.BR recipients were similar to those observed in unmanipulated, syngeneically reconstituted B10.BR-->B10.BR controls. This was not due to the inhibition of clonal proliferation by FK506, since 35 days after drug withdrawal complete recovery of the peripheral Thy1.2+ population was observed, while the percentages of V beta 5+ and V beta 11+Thy1.2+ T cells were maintained at values similar to controls. Surprisingly, clonal proliferation stimulated by monoclonal antibody against V beta 5 and V beta 11 TCRs was observed in CsA-treated, syngeneically reconstituted B10.BR mice but not in FK506-treated mice, suggesting that CsA may be more likely to induce autoreactivity. Differences in thymic architecture between FK506- and CsA-treated animals further suggested that the drugs may differ in their effects on T cell development in vivo.
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PMID:FK506 inhibits the differentiation of developing thymocytes but not negative selection of T cell receptor V beta 5+ and V beta 11+ T lymphocytes in vivo. 752 43

Background: Nerve regeneration in vascularized composite allotransplantation (VCA) is not well understood. Allogeneic transplant models experience complete loss of nerve tissue and axonal regeneration without immunosuppressive therapy. The purpose of this study was to determine the impact of incomplete immunosuppression on nerve regeneration. Methods: In this study, transgenic mice (4 groups in total) with endogenous fluorescent protein expression in axons (Thy1-YFP) and Schwann cells (S100-GFP) were used to evaluate axonal regeneration and Schwann cell (SC) migration in orthotopic-limb VCA models with incomplete immunosuppression using Tacrolimus (FK506). Survival and complication rates were assessed to determine the extent of tissue rejection. Nerve regeneration was assessed using serial imaging of axonal progression and SC migration and viability. Histomorphometry quantified the extent of axonal regeneration. Results: Incomplete immunosuppression with FK506 resulted in delayed rejection of skin, muscle, tendon, and bone in the transplanted limb. In contrast, the nerve demonstrated robust axonal regeneration and SC viability based on strong fluorescent protein expression by SCs and axons in transgenic donors and recipients. Total myelinated axon numbers measured at 8 weeks were comparable in all VCA groups and not statistically different from the syngeneic donor control group. Conclusions: Our data suggest that nerve and SCs are much weaker antigens compared with skin, muscle, tendon, and bone in VCA. To our knowledge, this study is the first to prove the weak antigenicity of nerve tissue in the orthotopic VCA mouse model.
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PMID:Robust Axonal Regeneration in a Mouse Vascularized Composite Allotransplant Model Undergoing Delayed Tissue Rejection. 2814 14