Effects of mycophenolate mofetil on the intestinal gamma delta T cells and expression of serum IL-6 and TNF-alpha in mice / 中华器官移植杂志

Objective To investigate the effect of mycophenolate mofetil (MMF) on the changes of intestinal gamma delta (γδ) T cells and the secretion of plasma IL-6 and TNF-α.Methods Adult male C57BL/6 (C57) mice were randomly divided into two groups by SAS 9.1.3 software:normal saline (NS) group and MMF group.The changes of γδ T cells in each intestinal segment of mice were detected by flow cytometry.ELISA was used to determine the levels of serum IL-6 and TNF-α.Results As compared with the NS group,the ratio of γδ T cells in the epithelial cell to lymphocyte (IEL) of the intestinal tract decreased,and the concentrations of plasma IL-6 and TNF-α increased in MFF group (P＜0.05 for all).Conclusion In mycophenolic acid-related enteritis,the proportion of γδ T cells in intestinal IEL decreased,and the secretion of IL-6 and TNF-α increased.

γδ T Cells Contribute to the Outcome of Murine Fulminant Viral Hepatitis via Effector Cytokines TNF-α and IFN-γ / 华中科技大学学报（医学）（英德文版）

The mechanisms involved in virus-induced severe hepatitis have not been fully elucidated.In this study,we investigated the role of gamma delta T cell receptors (γδ) T cells in the pathogenesis of fulminant viral hepatitis (FVH) induced by murine hepatitis virus strain 3 (MHV-3).The model of FVH was established by intraperitoneal injection of MHV-3 into Balb/cJ mice.The survival days of mice,and the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were examined.The proportions ofγδ T cells in blood,spleen and liver,and cytokines secreted by hepatic γδ T cells were analyzed by flow cytometry.The function of hepatic γδ T cells was examined by cytotoxicity assay.Balb/cJ mice died in 3 to 6 days post MHV-3 infection,with severe hepatic necrosis and significant augmentation of serum ALT and AST levels.The proportions of γδ T ceils in blood,spleen and liver were significantly increased post MHV-3 infection,while those of the early activating molecule CD69-expressing γδ T cells and productions of cytokines tumor necrosis factor-alpha (TNF-α) and interferon-γ (IFN-γ) increased remarkably in the liver.These highly activated liver γδ T cells were cytotoxic to MHV-3-infected hepatocytes in vitro and this effect of liver γδ T cells against hepatocytes might involve the TNF-α and IFN-γ pathway.These results demonstrated that γδ T cells might contribute to the pathogenesis ofMHV-3-induced FVH through the effector cytokines TNF-α and IFN-γ.

γδ T Cells Contribute to the Outcome of Murine Fulminant Viral Hepatitis via Effector Cytokines TNF-α and IFN-γ / 华中科技大学学报（医学）（英德文版）

The mechanisms involved in virus-induced severe hepatitis have not been fully elucidated.In this study,we investigated the role of gamma delta T cell receptors (γδ) T cells in the pathogenesis of fulminant viral hepatitis (FVH) induced by murine hepatitis virus strain 3 (MHV-3).The model of FVH was established by intraperitoneal injection of MHV-3 into Balb/cJ mice.The survival days of mice,and the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were examined.The proportions ofγδ T cells in blood,spleen and liver,and cytokines secreted by hepatic γδ T cells were analyzed by flow cytometry.The function of hepatic γδ T cells was examined by cytotoxicity assay.Balb/cJ mice died in 3 to 6 days post MHV-3 infection,with severe hepatic necrosis and significant augmentation of serum ALT and AST levels.The proportions of γδ T ceils in blood,spleen and liver were significantly increased post MHV-3 infection,while those of the early activating molecule CD69-expressing γδ T cells and productions of cytokines tumor necrosis factor-alpha (TNF-α) and interferon-γ (IFN-γ) increased remarkably in the liver.These highly activated liver γδ T cells were cytotoxic to MHV-3-infected hepatocytes in vitro and this effect of liver γδ T cells against hepatocytes might involve the TNF-α and IFN-γ pathway.These results demonstrated that γδ T cells might contribute to the pathogenesis ofMHV-3-induced FVH through the effector cytokines TNF-α and IFN-γ.

A Case of Successful Allogeneic Stem Cell Transplantation for Chemotherapy-refractory Hepatosplenic gamma delta-T Cell Lymphoma

Hepatosplenic T-cell lymphoma is a rare histologic type of peripheral T-cell lymphoma, which is characterized clinically by predominant involvement of the liver and spleen, with little or no adenopathy, and an often aggressive course. We experienced a case of a 44-year-old female who was diagnosed with hepatosplenic gamma delta T-cell lymphoma with bone marrow involvement. The patient was treated with multi- agent chemotherapy with Bortezomib plus CHOP (cyclophosphamide, vincristine, prednisone, doxorubicin), Alemtuzumab plus DHAP (dexamethasone, cisplatin, cytarabine), and IMVP-16 (Ifosfamide, MTX, etoposide); however, she failed to achieve partial remission. After salvage chemotherapy (GemOx: Gembicine, oxaliplatin, dexamethasone), she underwent allogeneic stem cell transplantation from an HLA sibling donor with one mismatch . The patient is currently living and has remained in complete remission for 6 months since transplantation.

Gamma/delta T lymphocytes in the BCG granulomatous lesions

Recent studies in man and animal models have demonstrated that TCR-gamma delta-bearing T cells (gamma delta T cells) are activated by mycobacteria and accumulate in the sites of mycobacterial infection. Although the function of gamma delta T cells remains unclear, some data suggest a potential role for these cells in the granulomatous immune response. To address the presence of gamma delta T cells within the BCG granulomas, we have characterized the TCR phenotype of T-lymphocytes present in the BCG granulomatous lesion immunohistochemically using a monoclonal antibody to TCR delta 1 and others. Fairly large numbers of gamma delta T cells were located at the periphery of the BCG granulomas without necrosis and most of them also expressed CD8. However, gamma delta T cells were rarely present in the granulomas with central caseous necrosis, calcification and fibrotic changes. With these results, it might be speculated that the CD8+ gamma delta T lymphocytes participate in the BCG granuloma formation mainly in the early stage.