CTLA4Ig Prevents Initiation but not Evolution of Anti-phospholipid Syndrome in NZW/BXSB Mice
| Autor: | Xiaobo Wang, Alla Akkerman, Michael P. Madaio, Lena Schiffer, Stephen M. Factor, Meera Ramanujam, Weiqing Huang, Anne Davidson |
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| Jazyk: | angličtina |
| Rok vydání: | 2004 |
| Předmět: |
Male
medicine.medical_specialty Immunoconjugates Time Factors T cell Immunology medicine.disease_cause Kidney Article Autoimmunity Abatacept Mice Immune system Monocytosis Adjuvants Immunologic Internal medicine medicine Immunology and Allergy Animals B cell Autoimmune disease biology business.industry Myocardium CD28 Heart medicine.disease Antiphospholipid Syndrome Flow Cytometry Disease Models Animal medicine.anatomical_structure Endocrinology biology.protein Female Antibody business |
| Popis: | NZW “ x ” BXSB F1 mice develop SLE that is associated with an anti-phospholipid syndrome characterized by anti-cardiolipin antibodies, thrombocytopenia and small coronary artery thrombosis. This syndrome is immune mediated and, dependent, on CD4+T cells. To determine whether disease in these mice can be treated with blockade of T cell costimulation we treated them with the CD28 antagonist CTLA4Ig at 9 or 12 weeks of age. CTLA4Ig completely prevented both SLE nephritis and myocardial infarcts if it was given at 9 weeks of age, before anti-cardiolipin antibodies could be detected in the serum and prevented both B cell expansion and activation and the development of peripheral monocytosis. If treatment was delayed until 12 weeks of age after cardiolipin antibodies had arisen but before the onset of clinical disease, CTLA4Ig had very little effect on disease progression. These findings indicate that CD4+T cell activation through CD28 is critical for disease initiation in this model but plays little role in disease progression or tissue damage. These findings have relevance to the treatment of anti-phospholipid syndrome in humans. |
| Databáze: | OpenAIRE |
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