CD4+ T cell lines with selective patterns of autoreactivity as well as CD4- CD8- T helper cell lines augment the production of idiotypes shared by pathogenic anti-DNA autoantibodies in the NZB x SWR model of lupus nephritis.
The (NZB x SWR)F1 hybrid mice (SNF1) uniformly develop lethal glomerulonephritis in marked contrast to their parents and produce nephritogenic autoantibodies that consist of highly cationic, IgG anti-DNA antibodies that share distinct cross-reactive idiotypes called IdLNF1 (idiotypes-lupus nephritis-SNF1). Herein we found that spleen cells of SNF1 mice at the late prenephritic stage, contained CD4+/CD8- and CD4-/CD8- Th that not only induced their B cells in vitro to produce highly cationic IgG autoantibodies to DNA but IdLNF1-positive IgG antibodies as well. The double-negative Th were unexpected in the SNF1 mice because they lack the lpr (lymphoproliferation) gene. We also derived IL-2-dependent CD4+/CD8- as well as CD4-/CD8- T cell lines from nephritic SNF1 mice, that could simultaneously induce IdLNF1-positive and cationic anti-DNA antibodies of IgG class. The CD4+ T cell lines consisted of "autoreactive" T cells, but not all of the lines were equal in autoantibody-inducing capability. Remarkably, the T cell lines that preferentially responded to F1-hybrid-MHC determinants, had a significantly greater ability to augment the production of pathogenic autoantibodies. The SNF1-Th could also augment autoantibody production by the NZB or SWR parent's B cells; however, IdLNF1-positive and cationic anti-DNA autoantibodies of IgG class were not induced, suggesting that the SNF1 mice possess a select population of inducible (susceptible) B cells that are committed to produce nephritogenic autoantibodies and the parental strains are deficient in such B cells. Thus, production of nephritogenic autoantibodies with IdLNF1 markers in the SNF1 mice could result from an interaction between a select population of B cells and CD4+ Th that preferentially recognize unique F1-hybrid-MHC determinants, as well as double-negative auxiliary Th.
Sainis
K
K
Department of Medicine, Tupper Research Institute, Boston, MA 02111.
Datta
S K
SK
D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis* / Q000502:physiology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D001323:Autoantibodies / Q000096:biosynthesis* / Q000502:physiology; D001402:B-Lymphocytes / Q000378:metabolism; D002460:Cell Line; D004247:DNA / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D007130:Immunoglobulin Idiotypes / Q000096:biosynthesis*; D008181:Lupus Nephritis / Q000209:etiology / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008806:Mice, Inbred AKR; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008814:Mice, Inbred NZB; D010641:Phenotype; D013045:Species Specificity; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D000974:Antibodies, Antinuclear; D000945:Antigens, Differentiation, T-Lymphocyte; D001323:Autoantibodies; D007130:Immunoglobulin Idiotypes; D004247:DNA