Journal
JOURNAL OF NEUROIMMUNE PHARMACOLOGY
Volume 5, Issue 2, Pages 176-188Publisher
SPRINGER
DOI: 10.1007/s11481-009-9181-3
Keywords
experimental autoimmune encephalomyelitis; functional avidity; tolerance; altered peptide ligands; MHC variant peptides; SHP-1
Categories
Funding
- NIH [R01 NS062358]
- National Multiple Sclerosis Society [RG 4047]
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [T32GM008169] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS071518, R01NS062358] Funding Source: NIH RePORTER
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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.
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