Induction of immunological tolerance to single-stranded and double-stranded DNA.

Single-stranded (ss) and double-stranded (ds) DNA were conjugated with the copolymers of d-glutamic acid and d-lysin (d-GL). Administration of ss-DNA-d-GL conjugates to C3H/H3 and NZB/W F1 mice could render the mice tolerant to both direct and indirect anti-ss-DNA antibody-forming cell responses, irrespective of their immune status. Repeated administration of ss-DNA- or ds-DNA-d-GL conjugates decreased the levels of anti-ss-DNA and anti-ds-DNA antibody titres and reduced the occurrence of ss-DNA and ds-DNA antibody-forming cells even in old female NZB/W F1 mice that had already developed an autoimmune state with lupus nephritis. The unresponsiveness was DNA-specific, and the state of tolerance was stable in vitro at the cellular level after the removal of the tolerogen. This tolerance model would be useful in analysing the regulatory mechanisms in anti-ss-DNA nd anti-ds-DNA antibody production, and application of this kind of therapy in the treatment of systemic lupus erythematosus is suggested.