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Carrier-Induced Tolerance to Nucleic Acid Antigens¹

From the Department of Biochemistry, Tufts University School of Medicine, Boston, Massachusetts 02111, and the Department of Medicine, Rheumatology/Immunology Service, Tufts New England Medical Center, Boston, Massachusetts 02111

Abstract

BALB/c and SJL mice were treated with nucleosides-IgG1 as a tolerogen, before either primary or secondary immunization with nucleosides-keyhole limpet hemocyanin. Nucleoside-specific responses were measured serologically by a modified Farr assay, with either ¹⁴C-labeled denatured DNA or nucleosides-¹³¹-I-labeled BSA as test antigen. Specificity of the response was tested by hapten inhibition experiments.

Multiple doses of nucleosides-IgG1 tolerogen given before the primary or secondary immunization effectively suppressed the secondary and tertiary anti-nucleoside responses. The tolerogen did not suppress the response to an unrelated hapten-KLH conjugate. The IgG alone did not suppress the anti-nucleoside response of BALB/c mice to nucleosides-KLH. Single doses of tolerogen before the primary or secondary immunization were less effective. Residual antibody in partially suppressed BALB/c mice showed changes in specificity as compared to controls. Suppression of the secondary response of SJL mice was measured much more readily by binding of nucleosides¹³¹-I-BSA than by binding of denatured DNA. This reflected an altered specificity of the residual antibody; in control animals, antibodies were directed against all four nucleosides, whereas the antibodies of partially suppressed animals were directed only against guanosine.

Suppression of anti-nucleic acid antibody responses may have therapeutic application in the management of systemic lupus erythematosus.

Footnotes

¹ This investigation was supported by National Institutes of Health Grant RO1-AI-11980, and in part by Massachusetts Heart Association Grant-in-Aid 1219, National Science Foundation Grant GB 37937, and the Arthritis Foundation (Massachusetts Chapter).