Within the last several years, exciting new avenues of potential immunotherapy of autoimmunity, have been described in animal models. Vaccination of rats with synthetic peptides corresponding to regions of T cell receptor beta chains have blocked subsequent development of EAE upon challenge with myelin basic protein. This model of T cell receptor peptide-based immunotherapy have recently been adapted to a mouse model in order to study and understand the mechanisms of this form of immunotherapy. A second form of potential immunotherapy has been based upon models of peptide-induced unresponsiveness. Projects outlined in this grant application intend to utilize these strategies of peptide- induced unresponsiveness in order to understand mechanisms of either T cell receptor peptide or immunodominant determinant peptide tolerance induction and to compare these models to the use of SEB to induce """"""""anergy"""""""" and to apply these strategies to the treatment of EAE. Such studies have relevance to potential immunotherapeutic protocols in man. Groups of experimental animals will be treated with synthetic peptides corresponding either to regions of the T cell receptor V(beta)8.2 or to the immunodominant determinants of MBP or with SEB. Not only will such immunized or vaccinated mice be studied, but adoptive transfer and treatment of transgenic animals expressing the T cell receptor alpha/beta heterodimer corresponding to the receptor expressed on an encephalitogenic T cell clone will be studied. Anergy arising in T cells following peptide-induced unresponsiveness will be analyzed and compared to SEB-induced anergy in vivo and to a model system of anergy developed in vitro using a novel molecular methodology termed differential display to identify candidate """"""""anergy genes."""""""" These studies may provide a cohesive foundation for the development of novel immunotherapeutic strategies for the treatment of multiple sclerosis.
| Samusik, Nikolay; Good, Zinaida; Spitzer, Matthew H et al. (2016) Automated mapping of phenotype space with single-cell data. Nat Methods 13:493-6 |
| Spitzer, Matthew H; Nolan, Garry P (2016) Mass Cytometry: Single Cells, Many Features. Cell 165:780-91 |
| Frei, Andreas P; Bava, Felice-Alessio; Zunder, Eli R et al. (2016) Highly multiplexed simultaneous detection of RNAs and proteins in single cells. Nat Methods 13:269-75 |
| Angelo, Michael; Bendall, Sean C; Finck, Rachel et al. (2014) Multiplexed ion beam imaging of human breast tumors. Nat Med 20:436-42 |
| Gottlieb, Peter; Utz, Paul J; Robinson, William et al. (2013) Clinical optimization of antigen specific modulation of type 1 diabetes with the plasmid DNA platform. Clin Immunol 149:297-306 |
| O'Gorman, William E; Dooms, Hans; Thorne, Steve H et al. (2009) The initial phase of an immune response functions to activate regulatory T cells. J Immunol 183:332-9 |
| Sachs, Karen; Itani, Solomon; Carlisle, Jennifer et al. (2009) Learning signaling network structures with sparsely distributed data. J Comput Biol 16:201-12 |
| Creusot, Remi J; Yaghoubi, Shahriar S; Chang, Pearl et al. (2009) Lymphoid-tissue-specific homing of bone-marrow-derived dendritic cells. Blood 113:6638-47 |
| Sachs, K; Itani, S; Fitzgerald, J et al. (2009) Learning cyclic signaling pathway structures while minimizing data requirements. Pac Symp Biocomput :63-74 |
| Creusot, Remi J; Yaghoubi, Shahriar S; Kodama, Keiichi et al. (2008) Tissue-targeted therapy of autoimmune diabetes using dendritic cells transduced to express IL-4 in NOD mice. Clin Immunol 127:176-87 |
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