Suppression of Ongoing T Cell-Mediated Autoimmunity by Peptide-MHC Class II Dimer Vaccination

Li Li, Zuoan Yi, Bo Wang, Roland Tisch
2009
Tissue-specific autoimmune diseases such as type 1 diabetes (T1D) are characterized by T cell-driven pathology. Administration of autoantigenic peptides provides a strategy to selectively target the pathogenic T cell response. Indeed, treatment with β cell peptides effectively prevents T1D in NOD mice. However, the efficacy of peptide immunotherapy generally wanes as β cell autoimmunity progresses and islet inflammation increases. With the goal of enhancing the efficacy of peptide
more » ... ptide immunotherapy, soluble (s)IAg7-Ig dimers covalently linked to β cell autoantigen-derived peptides were tested for the capacity to suppress late preclinical T1D. NOD female mice with established β cell autoimmunity were vaccinated i.v. with a short course of sIAg7-Ig dimers tethered to peptides derived from glutamic acid decarboxylase (GAD)65 (sIAg7-pGAD65). Treatment with sIAg7-pGAD65 dimers and the equivalent of only ~7 μg of native peptide effectively blocked the progression of insulitis and the development of diabetes. Furthermore, suppression of T1D was dependent on β cell-specific IL-10-secreting CD4+ T cells, although the frequency of GAD65-specific FoxP3-expressing CD4+ T cells was also increased in sIAg7-pGAD65 dimer vaccinated NOD mice. These results demonstrate that MHC class II-Ig dimer vaccination is a robust approach to suppress ongoing T cell-mediated autoimmunity, and may provide a superior strategy of adjuvant-free peptide-based immunotherapy to induce immunoregulatory T cells.
doi:10.17615/2565-rn77 fatcat:x7ow3qvztvch7mhzagdlu3vyhu