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Deaggregated homologous immunoglobulin-peptide conjugates induce peptide-specific T cell nonresponsiveness in vivo
1Medical Research Council Cellular Immunology Unit, Sir William Dunn School of Pathology, University of Oxford, GB. Benedict.Seddon@pathology.ox.ac.uk
Previous studies have proven the efficacy of intravenous injection of deaggregated 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 in complete Freund's adjuvant were completely protected from development of experimental allergic encephalomyelitis (EAE) by their injection with as little as 40 microg of peptide conjugate on days 0 and 10 after immunization. Peptide-specific proliferative and cytokine responses by T cells from treated rats in vitro were severely depressed compared with controls, while responses to whole MBP were unaffected. Significantly, injections of 100 microg of peptide conjugate on days 0 and 4 after adoptive transfer of peptide-specific T lines protected rats from passive EAE while a single injection of 100 microg of conjugate at the onset of active EAE prevented any further disease progression. Both results suggest that primed effector cells as well as naive T cells are prone to tolerance induction by this means. The ability to intervene in ongoing immune responses with such specificity may be useful therapeutically in control of autoimmunity or allergic responses to environmental antigens.
Previous studies have proven the efficacy of intravenous injection of deaggregated 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 in complete Freund's adjuvant were completely protected from development of experimental allergic encephalomyelitis (EAE) by their injection with as little as 40 microg of peptide conjugate on days 0 and 10 after immunization. Peptide-specific proliferative and cytokine responses by T cells from treated rats in vitro were severely depressed compared with controls, while responses to whole MBP were unaffected. Significantly, injections of 100 microg of peptide conjugate on days 0 and 4 after adoptive transfer of peptide-specific T lines protected rats from passive EAE while a single injection of 100 microg of conjugate at the onset of active EAE prevented any further disease progression. Both results suggest that primed effector cells as well as naive T cells are prone to tolerance induction by this means. The ability to intervene in ongoing immune responses with such specificity may be useful therapeutically in control of autoimmunity or allergic responses to environmental antigens.