Manipulating antigenic ligand strength to selectively target myelin-reactive CD4+ T cells in EAE.
The 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.
Sabatino
Joseph J
JJ
Department of Microbiology and Immunology, Emory University, 1510 Clifton Road, Atlanta, GA 30322, USA.
Rosenthal
Kristen M
KM
Evavold
Brian D
BD
D000818:Animals; D000915:Antibody Affinity; D000941:Antigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D005805:Genes, MHC Class I; D006801:Humans; D008024:Ligands; D009186:Myelin Sheath / Q000276:immunology*; D011485:Protein Binding; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism
D000941:Antigens; D008024:Ligands; D011948:Receptors, Antigen, T-Cell