Thymus dysfunction and chronic inflammatory disease in gp39 transgenic mice
| Autor: | J T Rulffes, Christopher H. Clegg, Alejandro Aruffo, D Hollenbaugh, I H Hoggatt, Harald S. Haugen, Andrew G. Farr, S K Durham |
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| Rok vydání: | 1997 |
| Předmět: |
Genetically modified mouse
Transgene Immunology CD40 Ligand Inflammation Cell Count Mice Transgenic Thymus Gland Biology Polymerase Chain Reaction Mice Immune system medicine Immunology and Allergy Animals CD40 Antigens CD40 Membrane Glycoproteins General Medicine Flow Cytometry Inflammatory Bowel Diseases Mice Inbred C57BL Thymocyte Lymphatic system medicine.anatomical_structure Gene Expression Regulation Chronic Disease biology.protein Bone marrow medicine.symptom |
| Zdroj: | International immunology. 9(8) |
| ISSN: | 0953-8178 |
| Popis: | Expression of gp39 on activated T cells provides a co-stimulatory signal in peripheral lymphoid tissue that regulates humoral and cell-mediated immunity. The function of gp39 and its receptor CD40 in thymus remains uncertain. Here we report that overexpression of gp39 in transgenic mouse thymus caused a dose-dependent decline in thymocyte numbers (.500 fold), loss of cortical epithelium and expansion of CD40 F medullary cells. Transplantation of transgenic bone marrow into normal mice indicated that gp39 significantly diminished thymocyte viability in the context of a ‘normal’ thymic environment. The peripheral tissues of transgenic mice also accumulated abnormalities in a transgene dose-dependent manner that involved inflammation and lymphoid tissue hypertrophy. Animals with the highest transgene copy numbers acquired a lethal inflammatory bowel disease marked by the infiltration of gp39 F T cells and CD40 F cells into diseased tissues. Examination of cells overexpressing gp39 suggested that these defects were caused, in part, by the saturation of a mechanism that sequesters gp39 inside non-activated cells and thus protects the immune system from inappropriate gp39‐CD40 interaction. These results establish a regulatory role for gp39 in thymus function and a causal relationship in mediating chronic inflammatory disease. |
| Databáze: | OpenAIRE |
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