The magnitude and encephalogenic potential of autoimmune response to MOG is enhanced in MOG deficient mice

Linares, D; Mana, P; Goodyear, M; Chow, AM; Clavarino, C; Huntington, ND; Barnett, L; Koentgen, F; Tomioka, R; Bernard, CCA; Freire-Garabal, M; Reid, HH

Author(s): Linares, D; Mana, P; Goodyear, M; Chow, AM; Clavarino, C; Huntington, ND; Barnett, L; Koentgen, F; Tomioka, R; Bernard, CCA; Freire-Garabal, M; Reid, HH;
Details: Publication Year 2003-12,Volume 21,Issue #4,Page 339-351
Journal Title: JOURNAL OF AUTOIMMUNITY
Publication Type: Journal Article
Abstract: Myelin oligodendrocyte glycoprotein (MOG) is a minor component of central nervous system myelin presumably implicated in the pathogenesis of Multiple Sclerosis (MS). Immunization with MOG leads to the development of Experimental Autoimmune Encephalomyelitis (EAE), the experimental model of MS. It has been suggested that its encephalitogenic potential may be due to the lack of MOG self-immune tolerance. To clarify this, we have generated a MOG deficient mouse (MOG(-/-)) strain. Surprisingly, MOG(35-55) specific proliferation and Th1-type cytokine production were markedly enhanced in MOG(-/-) mice compared to wild type control. Furthermore, adoptive transfer of MOG(35-55) specific T cells, isolated from MOG deficient mice, into wild-type recipients resulted in the development of a more severe disease, indicating a high capacity of MOG(-/-) T cells to initiate effector responses. Interestingly, T cell reactivity to overlapping MOG peptides in MOG(-/-) mice did not reveal new potential immunodominant epitopes in H-2(b) mice. Taken together, our data suggests that MOG self-tolerance modulates the encephalitogenic potential of autoreactive MOG T cells in the periphery. (C) 2003 Elsevier Ltd. All rights reserved.
Publisher: ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD
Keywords: MYELIN-OLIGODENDROCYTE GLYCOPROTEIN; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; T-CELL REPERTOIRE; BASIC-PROTEIN GENE; THYMIC EPITHELIAL-CELLS; CENTRAL-NERVOUS-SYSTEM; MULTIPLE-SCLEROSIS; IMMUNE-RESPONSES; LYMPHOID ORGANS; SELF-TOLERANCE
Publisher's Version: https://doi.org/10.1016/j.jaut.2003.09.001
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Creation Date: 2003-12-01 12:00:00