Exogenous Heat Shock Protein gp96 Ameliorates CD4+CD62L+ T-Cell–mediated Transfer Colitis
| Autor: | Anne Fischbeck, Michael Fried, Silvia Lang, Werner Falk, Isabelle Frey-Wagner, Gerhard Rogler, K. Schreiter, Martin Hausmann, Katharina Leucht |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
CD4-Positive T-Lymphocytes
medicine.medical_specialty T cell Mice SCID Major histocompatibility complex Mice Antigen Intestinal mucosa Antigens Neoplasm Heat shock protein Internal medicine medicine Animals Immunology and Allergy Intestinal Mucosa L-Selectin Antigen-presenting cell Cells Cultured Inflammation Mice Inbred BALB C Severe combined immunodeficiency biology Chemistry Macrophages Endoplasmic reticulum Gastroenterology Cell Differentiation Colitis Flow Cytometry medicine.disease Adoptive Transfer Endocrinology medicine.anatomical_structure biology.protein Female Spleen |
| Zdroj: | Inflammatory Bowel Diseases. 20:1933-1941 |
| ISSN: | 1078-0998 |
| Popis: | BACKGROUND: The heat shock protein gp96 is an endoplasmic reticulum chaperone involved in endoplasmic reticulum stress reactions. gp96 binds antigens and is secreted into extracellular space on cell stress. After reinternalization by antigen presenting cells, antigens can be transferred to major histocompatibility complex molecules. In recent studies, we found induction of gp96 during differentiation of intestinal macrophages, whereas it was absent in intestinal macrophages of patients with Crohn's disease. METHODS: To study immuno-modulating effects of gp96 in T-cell transfer colitis BALB/c donor mice were injected with 2 × 100 μg gp96. After 1 week, 2.5 × 10(5) CD4+CD62L+ cells were isolated from spleens and injected into severe combined immunodeficiency recipients. Another group received cells from untreated donors and was treated with 100 μg gp96 after transfer. Control groups received cells from untreated donors, or buffer alone. RESULTS: After transfer of CD4+CD62L+ T cells from gp96-pretreated donors, mice (TBT gp96) showed an initial weight loss, but after 3 weeks, they recovered and reached the starting weight after 5 weeks. Mice treated with gp96 after transfer (TAT gp96) showed a delayed weight loss in comparison with the CD4+CD62L+ group. The histological scores in CD4CD62L mice were 2.6 ± 0.1, in TBT gp96 mice 1.3 ± 0.3 (CD4+CD62L+ versus TBT gp96: P < 0.05) and in mice treated after transfer 1.9 ± 0.1 (CD4+CD62L+ versus TAT gp96: P < 0.05). CONCLUSIONS: These findings indicate an essential role of gp96 in the maintenance of tolerance against luminal antigens in the intestinal mucosa. The absence of gp96 in intestinal macrophages of patients with Crohn's disease might provoke loss of this tolerance mediating mechanism. |
| Databáze: | OpenAIRE |
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