Deaggregated homologous immunoglobulin-peptide conjugates induce peptide-specific T cell nonresponsiveness in vivo

Previous studies have proven the efficacy of intravenous injection of deagg regated protein as a means of inducing tolerance. In the present study, the immunodominant peptide 70-86 of myelin basic protein (MBP) was covalently linked to either mouse Ig or Lewis rat IgG. Lewis rats immunized with MBP i n complete Freund's adjuvant were completely protected from development of experimental allergic encephalomyelitis (EAE) by their injection with as li ttle as 40 mu g of peptide conjugate on days 0 and 10 after immunization. P eptide-specific proliferative and cytokine responses by T cells from treate d rats in vitro were severely depressed compared with controls, while respo nses to whole MBP were unaffected. Significantly, injections of 100 mu g of peptide conjugate on days 0 and 4 after adoptive transfer of peptide-speci fic T lines protected rats from passive EAE while a single injection of 100 mu g of conjugate at the onset of active EAE prevented any further disease progression. Both results suggest that primed effector cells as well as na ive T cells are prone to tolerance induction by this means. The ability to intervene in ongoing immune responses with such specificity may be useful t herapeutically in control of autoimmunity or allergic responses to environm ental antigens.