The hypothesis underlying this proposal is that """"""""regulatory"""""""" proteins, including interleukin-4 (IL-4), transforming growth factor beta (TGFbeta), interleukin-10 (IL-10), and/or products that bind TNFalpha including single chain variable fragments of monoclonal anti-TNFalpha or the soluble forms of the TNF receptor, delivered to """"""""autoimmune""""""""lesions in EAE by retroviral gene transduction of """"""""autoimmune"""""""" T cells with be therapeutic and ameliorate the disease. Studies outlined in this grant initially seek to examine this hypothesis by targeting """"""""regulatory"""""""" proteins to lesions of EAE through adoptive transfer of transduced T cells obtained from MBP- reactive TCR transgenic mice. If adoptive transfer studies are successful, targeted gene delivery using retroviral constructs in which the IL-2 ligand has been incorporated into the retroviral coat protein as a """"""""targeting"""""""" ligand for activated (CD25+) T cells will be attempted. Initial retargeting strategies will be attempted in vitro. If successful, these studies will be expanded in vivo in an attempt to target inflammatory T cells in lesions of EAE. There are five specific aims directed at: (1) vector development, retargeting methodology, and; (5) immunotherapy in vivo. The significance of these studies lies in their potential adaptation to immunotherapy not only of multiple sclerosis, but of other inflammatory autoimmune diseases.
| 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 |
| 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 |
| 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; 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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