Myelin Oligodendrocyte Glycoprotein-specific T Cell Receptor Transgenic Mice Develop Spontaneous Autoimmune Optic Neuritis

E. Bettelli, M. Pagany, H. L. Weiner, Christopher Linington, R. A. Sobel, V. K. Kuchroo

    Research output: Contribution to journalArticle

    499 Citations (Scopus)

    Abstract

    Multiple sclerosis (MS) is considered to be an autoimmune disease of the central nervous system (CNS) that in many patients first presents clinically as optic neuritis. The relationship of optic neuritis to MS is not well understood. We have generated novel T cell receptor (TCR) transgenic mice specific for myelin oligodendrocyte glycoprotein (MOG). MOG-specific transgenic T cells are not deleted nor tolerized and are functionally competent. A large proportion (>30%) of MOG-specific TCR transgenic mice spontaneously develop isolated optic neuritis without any clinical nor histological evidence of experimental autoimmune encephalomyelitis (EAE). Optic neuritis without EAE could also be induced in these mice by sensitization with suboptimal doses of MOG. The predilection of these mice to develop optic neuritis is associated with higher expression of MOG in the optic nerve than in the spinal cord. These results demonstrate that clinical manifestations of CNS autoimmune disease will vary depending on the identity of the target autoantigen and that MOG-specific T cell responses are involved in the genesis of isolated optic neuritis.

    Original languageEnglish
    Pages (from-to)1073-1081
    Number of pages8
    JournalJournal of Experimental Medicine
    Volume197
    DOIs
    Publication statusPublished - 2003

    Keywords

    • MOG
    • experimental autoimmune encephalomyelitis
    • multiple sclerosis
    • autoimmunity of CNS
    • disease model
    • EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS
    • CENTRAL-NERVOUS-SYSTEM
    • MULTIPLE-SCLEROSIS
    • PROTEOLIPID PROTEIN
    • BASIC-PROTEIN
    • ENCEPHALITOGENIC DETERMINANT
    • LEWIS RAT
    • SJL MICE
    • IDENTIFICATION
    • EXPRESSION

    Cite this

    Myelin Oligodendrocyte Glycoprotein-specific T Cell Receptor Transgenic Mice Develop Spontaneous Autoimmune Optic Neuritis. / Bettelli, E.; Pagany, M.; Weiner, H. L.; Linington, Christopher; Sobel, R. A.; Kuchroo, V. K.

    In: Journal of Experimental Medicine, Vol. 197, 2003, p. 1073-1081.

    Research output: Contribution to journalArticle

    Bettelli, E. ; Pagany, M. ; Weiner, H. L. ; Linington, Christopher ; Sobel, R. A. ; Kuchroo, V. K. / Myelin Oligodendrocyte Glycoprotein-specific T Cell Receptor Transgenic Mice Develop Spontaneous Autoimmune Optic Neuritis. In: Journal of Experimental Medicine. 2003 ; Vol. 197. pp. 1073-1081.
    @article{ac2f5092e4de404fb42b8771b1dbc8ab,
    title = "Myelin Oligodendrocyte Glycoprotein-specific T Cell Receptor Transgenic Mice Develop Spontaneous Autoimmune Optic Neuritis",
    abstract = "Multiple sclerosis (MS) is considered to be an autoimmune disease of the central nervous system (CNS) that in many patients first presents clinically as optic neuritis. The relationship of optic neuritis to MS is not well understood. We have generated novel T cell receptor (TCR) transgenic mice specific for myelin oligodendrocyte glycoprotein (MOG). MOG-specific transgenic T cells are not deleted nor tolerized and are functionally competent. A large proportion (>30{\%}) of MOG-specific TCR transgenic mice spontaneously develop isolated optic neuritis without any clinical nor histological evidence of experimental autoimmune encephalomyelitis (EAE). Optic neuritis without EAE could also be induced in these mice by sensitization with suboptimal doses of MOG. The predilection of these mice to develop optic neuritis is associated with higher expression of MOG in the optic nerve than in the spinal cord. These results demonstrate that clinical manifestations of CNS autoimmune disease will vary depending on the identity of the target autoantigen and that MOG-specific T cell responses are involved in the genesis of isolated optic neuritis.",
    keywords = "MOG, experimental autoimmune encephalomyelitis, multiple sclerosis, autoimmunity of CNS, disease model, EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS, CENTRAL-NERVOUS-SYSTEM, MULTIPLE-SCLEROSIS, PROTEOLIPID PROTEIN, BASIC-PROTEIN, ENCEPHALITOGENIC DETERMINANT, LEWIS RAT, SJL MICE, IDENTIFICATION, EXPRESSION",
    author = "E. Bettelli and M. Pagany and Weiner, {H. L.} and Christopher Linington and Sobel, {R. A.} and Kuchroo, {V. K.}",
    year = "2003",
    doi = "10.1084/jem.20021603",
    language = "English",
    volume = "197",
    pages = "1073--1081",
    journal = "Journal of Experimental Medicine",
    issn = "0022-1007",
    publisher = "Rockefeller University Press",

    }

    TY - JOUR

    T1 - Myelin Oligodendrocyte Glycoprotein-specific T Cell Receptor Transgenic Mice Develop Spontaneous Autoimmune Optic Neuritis

    AU - Bettelli, E.

    AU - Pagany, M.

    AU - Weiner, H. L.

    AU - Linington, Christopher

    AU - Sobel, R. A.

    AU - Kuchroo, V. K.

    PY - 2003

    Y1 - 2003

    N2 - Multiple sclerosis (MS) is considered to be an autoimmune disease of the central nervous system (CNS) that in many patients first presents clinically as optic neuritis. The relationship of optic neuritis to MS is not well understood. We have generated novel T cell receptor (TCR) transgenic mice specific for myelin oligodendrocyte glycoprotein (MOG). MOG-specific transgenic T cells are not deleted nor tolerized and are functionally competent. A large proportion (>30%) of MOG-specific TCR transgenic mice spontaneously develop isolated optic neuritis without any clinical nor histological evidence of experimental autoimmune encephalomyelitis (EAE). Optic neuritis without EAE could also be induced in these mice by sensitization with suboptimal doses of MOG. The predilection of these mice to develop optic neuritis is associated with higher expression of MOG in the optic nerve than in the spinal cord. These results demonstrate that clinical manifestations of CNS autoimmune disease will vary depending on the identity of the target autoantigen and that MOG-specific T cell responses are involved in the genesis of isolated optic neuritis.

    AB - Multiple sclerosis (MS) is considered to be an autoimmune disease of the central nervous system (CNS) that in many patients first presents clinically as optic neuritis. The relationship of optic neuritis to MS is not well understood. We have generated novel T cell receptor (TCR) transgenic mice specific for myelin oligodendrocyte glycoprotein (MOG). MOG-specific transgenic T cells are not deleted nor tolerized and are functionally competent. A large proportion (>30%) of MOG-specific TCR transgenic mice spontaneously develop isolated optic neuritis without any clinical nor histological evidence of experimental autoimmune encephalomyelitis (EAE). Optic neuritis without EAE could also be induced in these mice by sensitization with suboptimal doses of MOG. The predilection of these mice to develop optic neuritis is associated with higher expression of MOG in the optic nerve than in the spinal cord. These results demonstrate that clinical manifestations of CNS autoimmune disease will vary depending on the identity of the target autoantigen and that MOG-specific T cell responses are involved in the genesis of isolated optic neuritis.

    KW - MOG

    KW - experimental autoimmune encephalomyelitis

    KW - multiple sclerosis

    KW - autoimmunity of CNS

    KW - disease model

    KW - EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS

    KW - CENTRAL-NERVOUS-SYSTEM

    KW - MULTIPLE-SCLEROSIS

    KW - PROTEOLIPID PROTEIN

    KW - BASIC-PROTEIN

    KW - ENCEPHALITOGENIC DETERMINANT

    KW - LEWIS RAT

    KW - SJL MICE

    KW - IDENTIFICATION

    KW - EXPRESSION

    U2 - 10.1084/jem.20021603

    DO - 10.1084/jem.20021603

    M3 - Article

    VL - 197

    SP - 1073

    EP - 1081

    JO - Journal of Experimental Medicine

    JF - Journal of Experimental Medicine

    SN - 0022-1007

    ER -