Autoimmune neurologic diseases

Poster

Development of Eomes+ Helper T Cells in Association with Cns-derived Antigen-presenting Cells

Friday, June 16
6:15 PM - 7:30 PM

We have identified a previously unappreciated pathogenic CD4+ T cell subset expressing Eomes (Eomes+ Th cells) in a late/chronic course of experimental autoimmune encephalomyelitis (EAE) that presumably represent a secondary progressive multiple sclerosis (SPMS), a refractory subtype of MS. In the current study, we evaluated the role of antigen-presenting cells (APCs) accumulated in central nervous system (CNS) for induction or functional modification of Eomes+ Th cells in late/chronic EAE. First, we demonstrate that CNS APCs isolated from late EAE animals, including B cells and non-B/MHC class II+ cells, clearly promote Eomes expression in naïve splenic CD4+ T cells associated with enhanced cytotoxicity. Gene chip analysis reveals that numerous genes are differentially expressed in CNS APCs between early and late EAE. Among those differentially expressed genes, prolactin is upregulated only at late disease. Interestingly, exogenous prolactin induces Eomes expression in naïve splenic CD4+ T cells in vitro. Moreover, in vivo administration of an inhibitor for prolactin, Bromocriptin (BM), could effectively deley the onset and ameliorate severity of late EAE. In line with the clinical outcome, Eomes+ CD4+ T cells in CNS of late/chronic EAE are decreased in BM-treated mice and CNS APCs from the BM-treated mice show a defect in inducing Eomes expression in CD4+ T cells. Therefore, CNS APCs accumulated in CNS during late EAE facilitate the progression of chronic disease by means of promoting Eomes+ Th cells through the expression of prolactin. Collectively, treatments targeting prolactin may have a benefit for treating late/chronic disease of EAE and SPMS.

Chenyang Zhang

Department of Immunology, National Institute of Neuroscience, NCNP

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    Shinji Oki

    Department of Immunology, National Institute of Neuroscience, NCNP

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      Ben Raveney

      Department of Immunology, National Institute of Neuroscience, NCNP

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        Takashi Yamamura

        Department of Immunology, National Institute of Neuroscience, NCNP, Japan

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          Development of Eomes+ Helper T Cells in Association with Cns-derived Antigen-presenting Cells



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