Induction of systemic lupus erythematosus in naive mice with T-cell lines specific for human anti-DNA antibody SA-1 (16/6 Id+) and for mouse tuberculosis antibody TB/68 (16/6 Id+).
Previously we have shown the ability to induce experimental systemic lupus erythematosus (SLE) in naive mice with pathogenic antibodies carrying the 16/6 idiotype (Id) and with the T-cell line specific for the 16/6 Id. In the present study we established and characterized a series of T-cell clones that react against diverse autoantibodies carrying the 16/6 Id and show that they are capable of inducing a SLE-like disease in mice. The T-cell clones were generated from BALB/c mice immunized with the human mAb anti-DNA antibody (SA-1) and the mouse monoclonal anti-tuberculous Ab (TB/68), both carrying the 16/6 Id. The T-cell clones proliferated only in the presence of either human or mouse mAb carrying the 16/6 Id. All the T-cell clones were found to be of the helper type (L3T4) and were H-2 restricted in their function. The injection of the clones to BALB/c mice resulted in serological findings (e.g., anti-DNA, anti-Sm), clinical manifestations (e.g., proteinuria, low white blood cell counts, increased erythrocyte sedimentation rate), and renal insult typical of SLE disease. Our data support the role attributed to pathogenic idiotypes in SLE on the one hand and that played by cellular immunity on the other. The mechanism by which Id-specific T-helper cells may induce SLE is currently not clear. The immunogenicity of the T-cell receptor (anti-16/6) and the cells themselves acting as effector/helper cells, thus leading to damage, may play a role in initiating a chain of events that ends in the production of a panoply of autoantibodies, some of which may also have a regulatory function.
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Department of Medicine B, Chaim Sheba Medical Center, Tel-Hashomer, Israel.
Mendlovic
S
S
Mozes
E
E
Coates
A R
AR
Shoenfeld
Y
Y
D000818:Animals; D000974:Antibodies, Antinuclear / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000917:Antibody Formation; D000918:Antibody Specificity; D002999:Clone Cells / Q000276:immunology; D005260:Female; D006801:Humans; D007130:Immunoglobulin Idiotypes / Q000276:immunology; D016219:Immunotherapy, Adoptive; D008180:Lupus Erythematosus, Systemic / Q000209:etiology* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D013601:T-Lymphocytes / Q000166:cytology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D014376:Tuberculosis / Q000276:immunology*
D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D007130:Immunoglobulin Idiotypes