Fas/Fas ligand pathway, apoptosis, and clonal anergy involved in systemic acetylcholine receptor T cell epitope tolerance

C Deng, E Goluszko, P Christadoss - The Journal of Immunology, 2001 - journals.aai.org
C Deng, E Goluszko, P Christadoss
The Journal of Immunology, 2001journals.aai.org
The cellular mechanisms of high dose systemic acetylcholine receptor (AChR) T cell
epitope, α146–162 peptide-induced tolerance in experimental myasthenia gravis were
examined. CD4 cells are the prime target for α146–162 peptide-induced tolerance. The
expression of CD69, Fas, and B7. 2 molecules on AChR-immune lymphocytes was
enhanced within 4–12 h after tolerance induction. A high dose of α146–162 peptide in IFA
failed to suppress T cell proliferation and/or clinical myasthenia gravis in lpr and gld mice …
Abstract
The cellular mechanisms of high dose systemic acetylcholine receptor (AChR) T cell epitope, α146–162 peptide-induced tolerance in experimental myasthenia gravis were examined. CD4 cells are the prime target for α146–162 peptide-induced tolerance. The expression of CD69, Fas, and B7. 2 molecules on AChR-immune lymphocytes was enhanced within 4–12 h after tolerance induction. A high dose of α146–162 peptide in IFA failed to suppress T cell proliferation and/or clinical myasthenia gravis in lpr and gld mice deficient in Fas and Fas ligand, respectively. A high dose of α146–162 peptide in IFA in AChR-immunized mice induced apoptosis of BV6 cells. Further, reconstitution of IL-2 in vitro-recovered α146–162 peptide tolerized T cell proliferation, IFN-γ, and IL-10 production. The findings implicate the possible role of Fas-/Fas ligand-mediated apoptosis and the resulting clonal anergy as the mechanisms of high dose AChR α146–162 peptide-induced tolerance on CD4 cells.
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