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lüll Manipulating antigenic ligand strength to selectively target myelin-reactive CD4+ T cells in EAE Sabatino JJ Jr; Rosenthal KM; Evavold BDJ Neuroimmune Pharmacol 2010[Jun]; 5 (2): 176-88The development of antigen-specific therapies for the selective tolerization of autoreactive T cells remains the Holy Grail for the treatment of T-cell-mediated autoimmune diseases such as multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE). This quest remains elusive, however, as the numerous antigen-specific strategies targeting myelin-specific T cells over the years have failed to result in clinical success. In this review, we revisit the antigen-based therapies used in the treatment of myelin-specific CD4+ T cells in the context of the functional avidity and the strength of signal of the encephalitogenic CD4+ T cell repertoire. In light of differences in activation thresholds, we propose that autoreactive T cells are not all equal, and therefore tolerance induction strategies must incorporate ligand strength in order to be successful in treating EAE and ultimately the human disease MS.|Animals[MESH]|Antibody Affinity[MESH]|Antigens/*immunology[MESH]|CD4-Positive T-Lymphocytes/*immunology[MESH]|Encephalomyelitis, Autoimmune, Experimental/*immunology[MESH]|Genes, MHC Class I[MESH]|Humans[MESH]|Ligands[MESH]|Myelin Sheath/*immunology[MESH]|Protein Binding[MESH]|Receptors, Antigen, T-Cell/metabolism[MESH] |