8388689

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2

To further understand the contribution of I-A to the development of disease in murine lupus, we compared the incidence and/or titers of natural thymocytotoxic autoantibodies (NTAs), autoantibodies to red blood cells, gp70 immune complexes (gp70), antibodies to Sm, and rheumatoid factor in NZB (H-2d), NZB.H-2b and NZB.H-2bm12 mice. There were striking and significant differences among the three NZB strains in several of these parameters. NZB (H-2d) and NZB.H-2bm12 mice had a 100% incidence of NTA. In contrast, NZB.H-2b mice were found to have NTA in only 36% of animals at 8-10 months of age. Furthermore, the NTA titers of NZB.H-2bm12 mice were relatively low. There were also distinct differences between these strains with respect to the presence of antibodies to anti-erythrocytes (positive Coombs' test). NZB (H-2d) and NZB.H-2bm12 both had high titers of anti-erythrocyte autoantibodies (AEAs), whereas there was a delayed onset and lower titers in NZB.H-2b mice. Additionally, there was a dramatic increase in gp70 IC levels in NZB.H-2bm12 mice. In previous studies, NZB.H-2bm12 as well as NZB.H-2bm12 x NZB.H-2b F1 mice were found to produce high autoantibody titers to single-stranded (ss) and double-stranded (ds) DNA. Using unfractionated or fractionated splenic T cells (CD4+ CD8-, CD4- CD8+, or CD4-CD8-) from NZB.H-2b or NZB.H-2bm12 mice, we compared their relative abilities to cooperate with T-depleted splenocytes from NZB.H-2bm12 x NZB.H-2b F1 mice to produce antibodies to ss- and ds-DNA. Only T cells, including both CD4+ CD8- and CD4- CD8- populations, from NZB.H-2bm12 mice, were able to induce such autoantibody production among F1 splenocytes. Finally, marked alterations in splenic T cell subsets were found in NZB.H-2bm12 mice compared to NZB.H-2b mice, and to a lesser extent, in B6.C-H-2bm12 mice compared to C57BL/6 (H-2b) mice. These data further highlight the influence of I-A on autoimmunity and in particular the influence of the bm12 mutation on altering the natural history of disease expression in NZB mice.

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0896-8411

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131-43

pubmed-meshheading:8388689-Animals, pubmed-meshheading:8388689-Antigen-Antibody Complex, pubmed-meshheading:8388689-Autoantibodies, pubmed-meshheading:8388689-Autoantigens, pubmed-meshheading:8388689-Autoimmune Diseases, pubmed-meshheading:8388689-Erythrocytes, pubmed-meshheading:8388689-Genes, MHC Class II, pubmed-meshheading:8388689-Glycoproteins, pubmed-meshheading:8388689-H-2 Antigens, pubmed-meshheading:8388689-Hemagglutinins, pubmed-meshheading:8388689-Histocompatibility Antigens Class II, pubmed-meshheading:8388689-Lupus Erythematosus, Systemic, pubmed-meshheading:8388689-Mice, pubmed-meshheading:8388689-Mice, Inbred NZB, pubmed-meshheading:8388689-Phenotype, pubmed-meshheading:8388689-Rheumatoid Factor, pubmed-meshheading:8388689-Ribonucleoproteins, Small Nuclear, pubmed-meshheading:8388689-T-Lymphocyte Subsets, pubmed-meshheading:8388689-snRNP Core Proteins

The contribution of I-Abm12 to phenotypic and functional alterations among T-cell subsets in NZB mice.

Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't