Antibody-mediated regulation of the response to a protective cryptic epitope in rMOG-induced EAE (BA8P.166)

Abstract

Abstract Multiple sclerosis is a Th1/Th17-mediated autoimmune disease of the central nervous system, in which B cells are involved. Experimental autoimmune encephalomyelitis (EAE) is the main animal model for MS. Previously we showed that B cell-deficient (B-/-) mice were resistant to rMOG-induced EAE. Further investigation revealed response to a cryptic epitope (MOG61-85) by lymph node (LN) T cells from rMOG-immunized B-/- mice but not WT mice. We investigated the immune response to MOG61-85 and the role of antibody in altering this response. EAE was ameliorated in B-/- mice when coimmunized with MOG35-55 and MOG61-85 compared with MOG35-55 alone. B-/- mice immunized with both peptides and injected with rabbit serum primed to MOG35-55 and MOG61-85 developed more severe EAE with earlier onset than mice receiving preimmune rabbit serum. Purified IgG from rMOG primed WT mice added to cultured LN T cells from co-immunized B-/- mice decreased T cell proliferation to MOG61-85, indicating that antibody inhibited the T cell response to MOG61-85. ELISA of culture supernatants from rMOG-primed WT LN cells demonstrated presence of TGF-β but not IL6 in response to MOG61-85; both cytokines were present in response to MOG35-55. B cell-/- LN cells cultured with MOG61-85 vs. MOG35-55 showed similar percentages of CD4+CD25+FoxP3+ T cells, whereas CD8+CD25+ T cells were slightly increased in those cultured with MOG61-85. The characterization of this CD8+ population is still under investigation.