Induction of nonpathologic, humoral autoimmunity in lupus-prone mice by a class II-restricted, transgenic alpha beta T cell. Separation of autoantigen-specific and -nonspecific help
| Autor: | S L Peng, S Fatenejad, J Craft |
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| Rok vydání: | 1996 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 157:5225-5230 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.157.12.5225 |
| Popis: | Murine lupus predominantly requires alpha beta T cells, which provide pathogenic help for autoantibody production and immune complex-associated end-organ disease. Autoantigen-specific, pathogenic alpha beta T cells have been isolated from some lupus-prone mice, but a requirement for such T cells in disease has not been clearly demonstrated. To address alpha beta T cell specificity in murine lupus, lupus-prone mice were generated that contained only a single population of alpha beta T cells of foreign specificity by generating anti-pigeon cytochrome c (AND) TCR transgenic TCRalpha -/- TCRbeta -/- MRL/Mp-lpr/lpr (MRL/lpr) mice, which lacked the ability to express endogenous TCRalpha or -beta genes. These AND alpha beta T cells induced hypergammaglobulinemia and autoantibody production, as seen in serum Ig, anti-DNA, anti-small nuclear ribonucleoprotein (snRNP) and rheumatoid factor titers, but failed to promote the development of lymphadenopathy or pathogenic immune-complex disease, as assayed by cutaneous, renal, and salivary gland lesions. Thus, antigen-nonspecific alpha beta T cell help can promote generalized autoimmunity, but autoantigen-specific alpha beta T cells are required to cause overt disease. |
| Databáze: | OpenAIRE |
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