The assessment of anti-idiopathic antibodies as effective immunoregulatory probes in vivo.

In order to increase our understanding of the potential to use anti-idiotypic antibodies as immune modulators in vivo, we extensively analysed influences induced by one such antibody (anti-Id-l) following its administration to animals of different ages, genetic backgrounds, and immunological histories. Id-l is an inter-strain idiotype associated with rat anti-Group A streptococcal carbohydrate antibodies. The intraperitoneal (i.p.) injection of anti-Id-l antibodies, prepared against Id-l+ antibodies from an HPR rat could effectively induce long-term idiotype suppression in all tested strains of rats, regardless of the age at the time of treatment, the RTl haplotype or IgG2c or k-chain allotype. Total anti-streptococcal antibodies were not suppressed by this treatment. Although long-term suppression could be induced at any age, the percentage of animals suppressed following neonatal injections was consistently less than that following adult injections of anti-idiotypic antibodies. In addition, neonatal injections of anti-Id-l or Id-l with anti-Id-l appeared to enhance Id-l production in a minority of the animals. Similar treatment of adult animals never increased Id-l synthesis, suggesting that cells associated with enhanced Id-l production in older animals are either refractory to activation-differentiation signals and/or are sequestered and no longer accessible by i.v. or i.p. routes of administration of the probe. Auto-anti-Id-l immunity induced by immunizing adult rats with heavy, light, F(ab')2 fragments or whole IgG molecules could also induce an Id-l suppressed state. We were not able to induce significant Id-l suppression if animals were immunized with antigen prior to the injection of anti-Id-l. There was evidence, however, that such treatment might lead in time to the development of some idiotype specific suppression.