Myelin oligodendrocyte glycoprotein–specific T and B cells cooperate to induce a Devic-like disease in mice
Estelle Bettelli, Dominique Baeten, Anneli Jäger, Raymond A. Sobel, Vijay K. Kuchroo
Estelle Bettelli, Dominique Baeten, Anneli Jäger, Raymond A. Sobel, Vijay K. Kuchroo
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Research Article Autoimmunity

Myelin oligodendrocyte glycoprotein–specific T and B cells cooperate to induce a Devic-like disease in mice

Abstract

Multiple sclerosis (MS) is a clinically and pathologically heterogeneous inflammatory/demyelinating disease of the CNS. In the MS variant Devic disease, lesions are predominantly found in the optic nerves and spinal cord but not the brain. The immunological bases of the different forms of MS are unknown. We previously generated myelin oligodendrocyte glycoprotein–specific (MOG-specific) TCR transgenic mice (TCRMOG mice; also referred to as 2D2 mice) and reported that a large proportion of these mice develop spontaneous isolated optic neuritis. We have now crossed the TCRMOG mice with MOG-specific Ig heavy-chain knock-in mice (IgHMOG mice; also referred to as Th mice), in which one-third of the B cells are specific for MOG. In these mice, MOG-specific B cells are very efficient in presenting MOG to the transgenic T cells and undergo class switching to IgG1 in the presence of the transgenic T cells. Sixty percent of TCRMOG×IgHMOG mice spontaneously developed a severe form of experimental autoimmune encephalomyelitis (EAE). Histological examination of the CNS revealed a selective distribution of meningeal and parenchymal inflammatory lesions in the spinal cord and optic nerves. Thus, CNS antigen–specific T and B cells cooperate to induce a distinct clinicopathologic EAE pattern that closely replicates human Devic disease.

Authors

Estelle Bettelli, Dominique Baeten, Anneli Jäger, Raymond A. Sobel, Vijay K. Kuchroo

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Figure 5

IL-17– and IFN-γ–producing CD4+ T cells infiltrate the CNS of TCRMOG ×IgHMOG mice with Devic disease.

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IL-17– and IFN-γ–producing CD4+ T c...
(A) Mononuclear cells from the brains and spinal cords of WT and IgHMOG mice as well as healthy and sick TCRMOG×IgHMOG mice were isolated by percoll gradient and stained with anti-CD4 antibody. Dot plots show CD4 expression versus side scatter (SSC). The percentage of CD4+ T cells present in the gate is indicated. (B) Mononuclear cells isolated from the brains and spinal cords of TCRMOG×IgHMOG mice with Devic disease were stimulated with PMA and ionomycin, and the presence of IL-17– and IFN-γ–secreting CD4+ T cells was determined by intracellular cytokine staining. The percentage of IL-17– and IFN-γ–positive and –negative cells in CD4+ T cells is indicated in each dot plot. (C) RNA was prepared from the spinal cords of TCRMOG mice with EAE (n = 2) and TCRMOG×IgHMOG mice with Devic-like disease (n = 2). Expression of IL-17 and IFN-γ cDNAs was determined by real-time PCR, and results are expressed as relative to β-actin.