Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0409974 (lupus)
 22,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID: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. 895 66

Autoantigen presentation to T cells is crucial for the development of autoimmune disease. However, the mechanisms of autoantigen presentation are poorly understood. In this study, we show that splenic phagocytes play an important role in autoantigen presentation in murine lupus. Nucleosomes are major autoantigens in systemic lupus erythematosus. We found that nucleosome-specific T cells were stimulated dominantly in the spleen, compared with lymph nodes, lung, and thymus. Among splenic APCs, F4/80(+) macrophages and CD11b(+)CD11c(+) dendritic cells were strong stimulators for nucleosome-specific T cells. When splenic phagocytes were depleted in (NZB x NZW) F(1) (NZB/W F(1)) mice, nucleosome presentation in the spleen was dramatically suppressed. Moreover, depletion of splenic phagocytes significantly suppressed anti-nucleosome Ab and anti-dsDNA Ab production. Proteinuria progression was delayed and survival was prolonged in phagocyte-depleted mice. The numbers of autoantibody- secreting cells were decreased in the spleen from phagocyte-depleted mice. Multiple injections of splenic F4/80(+) macrophages, not those of splenic CD11c(+) dendritic cells, induced autoantibody production and proteinuria progression in NZB/W F(1) mice. These results indicate that autoantigen presentation by splenic phagocytes including macrophages significantly contributes to autoantibody production and disease progression in lupus-prone mice.
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PMID:Splenic phagocytes promote responses to nucleosomes in (NZB x NZW) F1 mice. 1883 81