Interferon-gamma is required during the initiation of an organ-specific autoimmune disease
| Autor: | Ban-Hock Toh, Paul A. Gleeson, Simon P. Barrett, Ian R. van Driel, Harini D De Silva |
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| Rok vydání: | 1996 |
| Předmět: |
Pathology
medicine.medical_specialty Autoimmune Gastritis medicine.medical_treatment Immunology Dose-Response Relationship Immunologic medicine.disease_cause Autoimmunity Autoimmune Diseases Interferon-gamma Mice Gastric mucosa Immunology and Allergy Medicine Animals Autoimmune disease Mice Inbred BALB C business.industry Autoantibody Antibodies Monoclonal medicine.disease Thymectomy Gastric chief cell medicine.anatomical_structure Animals Newborn Organ Specificity Gastritis medicine.symptom business Spleen |
| Zdroj: | European journal of immunology. 26(7) |
| ISSN: | 0014-2980 |
| Popis: | Autoimmune gastritis induced by neonatal thymectomy of mice is a CD4+ T cell-mediated organ-specific autoimmune disease. The characteristic features of autoimmune gastritis, which include a mononuclear infiltrate within the gastric mucosa, loss of parietal and chief cells and circulating autoantibodies to the gastric H+/K+ ATPase, appear 6-10 weeks after thymectomy. Here we have assessed the role of interferon-gamma (IFN-gamma) in the pathogenesis of the gastric lesion. Splenic T cells derived from mice with gastritis produced three- to tenfold more IFN-gamma than T cells from normal animals after stimulation with anti-CD3 antibodies. Treatment of neonatally thymectomized mice at weekly intervals for 6 or 12 weeks with a neutralizing rat monoclonal antibody to mouse IFN-gamma abolished the production of anti-gastric autoantibodies and decreased the incidence of gastric mononuclear infiltrates from the 69% observed in normal rat immunoglobulin (Ig)-injected mice to 16%. Further, in mice treated with only a single dose of anti-IFN-gamma immediately after thymectomy at 3 days after birth, the incidence of autoimmune gastritis was 1/19 compared to 8/19 in normal rat Ig-injected mice. Prevention of autoimmunity by neutralization of IFN-gamma several weeks prior to the detection of a pathological lesion strongly suggests that IFN-gamma plays an essential role in the initiation of the gastric autoimmune response. |
| Databáze: | OpenAIRE |
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