The contribution of I-Abm12 to phenotypic and functional alterations among T-cell subsets in NZB mice.
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.
Naiki
M
M
Division of Rheumatology, Allergy and Clinical Immunology, University of California, School of Medicine, Davis 95616.
Yoshida
S H
SH
Watanabe
Y
Y
Izui
S
S
Ansari
A A
AA
Gershwin
M E
ME
D000818:Animals; D000936:Antigen-Antibody Complex / Q000097:blood / Q000276:immunology; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology*; D004912:Erythrocytes / Q000276:immunology; D005802:Genes, MHC Class II; D006023:Glycoproteins / Q000276:immunology*; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology; D006388:Hemagglutinins / Q000097:blood; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008814:Mice, Inbred NZB / Q000235:genetics / Q000276:immunology*; D010641:Phenotype; D012217:Rheumatoid Factor / Q000097:blood; D017411:Ribonucleoproteins, Small Nuclear; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D055517:snRNP Core Proteins
D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D001324:Autoantigens; D006023:Glycoproteins; D006183:H-2 Antigens; D006388:Hemagglutinins; D000949:Histocompatibility Antigens Class II; D017411:Ribonucleoproteins, Small Nuclear; C033589:glycoprotein gp70, murine serum; D055517:snRNP Core Proteins; D012217:Rheumatoid Factor