Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.48 (transcriptase)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Autoimmune hepatitis (AIH) is characterized by dense T-cell infiltrations in the liver tissue, but little is known how T cells influence the pathogenesis. To address this question, the distribution of T-cell receptor variable beta-chain (TCR Vbeta) transcripts of peripheral blood and liver-infiltrating T cells from previously untreated patients with newly diagnosed acute exacerbated AIH was investigated. Furthermore, the lengths and sequences of complementary-determining region 3 (CDR3) were studied. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis and CDR3 spectratyping revealed multiple clonal expansions of liver-infiltrating T cells but not peripheral T cells within various TCR Vbeta families. Further analysis of overexpressed TCR Vbeta transcripts using TCR beta-chain-joining element (TCR Jbeta)-specific primers in a nested PCR showed characteristic Vbeta/Jbeta combinations. Subsequent sequencing of CDR3 regions from PCR products confirmed the clonality of T-cell expansions and the usage of common and individual CDR3 motifs. In conclusion, the clonality of expanded T cells within the liver tissue during early clinical manifestation of untreated AIH indicated that autoantigen-specific T cells accumulate at the inflammation site. Individual and common CDR3 motifs argued for predominant epitopes that were recognized by liver-infiltrating T cells in AIH patients.
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PMID:Individual and common antigen-recognition sites of liver-derived T cells in patients with autoimmune hepatitis. 1266 2

Engagement of the TCR without appropriate costimulation will result in the inability of T-cells to respond to the alloantigen as described earlier. We made a further investigation into the effect of relieving graft-versus-host disease (GVHD) and its mechanism in mice by blocking CD137-CD137L pathway in vitro. Responder cells (spleen cells) from BALB/C donor mice (H-2d) were incubated with stimulator cells (spleen cells) from C57BL/6 recipient mice (H-2b), with or without anti-CD137L monoclonal antibodies (MoAbs). Donor bone marrow cells plus mixed lymphocyte culture (MLC) T-cells were transplanted into lethally irradiated C57BL/6 mice. C57BL/6 mice were divided into 3 groups: group A (allogeneic bone marrow transplantation control group), group B (cyclosporine + methotrexate group), and group C (donor T-cells were treated with anti-CD137L MoAbs). The percentage of CD3+CD4+ and CD3+CD8+ T-cells were detected by flow cytometry, and the levels of cytokines (IFN-gamma, interleukin [IL]-2, IL-10, IL-4) by reverse-transcriptase polymerase chain reaction. The incidence of GVHD in group C was 70%, while the incidence of GVHD was 100% in group A and group B. The survival rate of group C was higher than that of group A and B, and the median survival time was longer than that of group A and B (P < .01). Clinical symptoms and histological signs of GVHD in group C were the mildest among all 3 groups. The percentage of CD3+CD8+T-cells in group C was lower than that in group A and B (P < .01). The levels of IFN-gamma in group C were markedly lower than those in group A and B (P < .01), and the levels of IL-10 in group C were significantly higher than those in group A and B (P < .01). The results suggest that treatment of donor T-cells by anti-CD137L MoAbs in vitro may relieve GVHD, thereby improve the survival time and survival rate of recipient mice, which might be related to the increased TH1 cytokine (IFN-gamma) and decreased TH2 cytokine (IL-10) as well as the reduced CD3+CD8+T-cells.
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PMID:Study of relieving graft-versus-host disease by blocking CD137-CD137 ligand costimulatory pathway in vitro. 1767 73

This study was purposed to investigate the dynamic change of clonal proliferation of T cell receptor V subfamilies in peripheral blood of patients received allo-hematopoietic stem cell transplantation (allo-HSCT) and to analyze the relationship between T cell clonal proliferative changes and GVHD. The peripheral blood mononuclear cell samples from 70 cases (17 GVHD patients) undergoing allo-PBCST patients were detected for CDR3 (complementarity determining region 3 repertoire analysis of T cell receptor Vbetagene) using reverse-transcriptase-polymerase chain reaction (RT-PCR). The products were further analyzed by genescan to identify T cell clonality. The results showed that the patients of HSCT generally passed through a transformation from monoclone to polyclone. At day 60 - 90 after HSCT, half of the cases were monoclonal and the remainders were polyclonal. After 120 days, most of patients without GVHD transferred into polyclones, however, patients with GVHD remained monoclonal after one year because of immunosuppressive agents and GVHD itself. The peripheral blood of GVHD patients mainly expressed monoclone/biclone at the time of target organ damage conspicuously, after medication intervention, partial monoclone or bioclone expressed TCR Vbeta subfamilies were diverted to polyclonal expression. It is concluded that the T cells present clonal proliferation and T cell receptors are prone to be used when patients are in earlier period of transplantation or with GVHD especially. The expression of TCR Vbeta subfamilies can return to normal polycloning along with the recovery of hematopoiesis and immunity in patients.
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PMID:[Clonal kinetic proliferative change of TCR Vbeta subfamilies in peripheral blood of patients transplanted with allogeneic hematopoietic stem cells and its relation to GVHD]. 1770 6


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