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J Neuroinflammation. 2020 Feb 19;17(1):68. doi: 10.1186/s12974-019-1676-0.

c-Met is expressed by highly autoreactive encephalitogenic CD8+ cells.

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Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
Department of Neurosciences, Division of Neurology, University Hospital of Geneva, Geneva, Switzerland.



CD8+ T lymphocytes are critical mediators of neuroinflammatory diseases. Understanding the mechanisms that govern the function of this T cell population is crucial to better understanding central nervous system autoimmune disease pathology. We recently identified a novel population of highly cytotoxic c-Met-expressing CD8+ T lymphocytes and found that hepatocyte growth factor (HGF) limits effective murine cytotoxic T cell responses in cancer models. Here, we examined the role of c-Met-expressing CD8+ T cells by using a MOG35-55 T cell-mediated EAE model.


Mice were subcutaneously immunized with myelin oligodendrocyte glycoprotein peptide (MOG)35-55 in complete Freund's adjuvant (CFA). Peripheral and CNS inflammation was evaluated at peak disease and chronic phase, and c-Met expression by CD8 was evaluated by flow cytometry and immunofluorescence. Molecular, cellular, and killing function analysis were performed by real-time PCR, ELISA, flow cytometry, and killing assay.


In the present study, we observed that a fraction of murine effector CD8+ T cells expressed c-Met receptor (c-Met+CD8+) in an experimental autoimmune encephalitis (EAE) model. Phenotypic and functional analysis of c-Met+CD8+ T cells revealed that they recognize the encephalitogenic epitope myelin oligodendrocyte glycoprotein37-50. We demonstrated that this T cell population produces higher levels of interferon-γ and granzyme B ex vivo and that HGF directly restrains the cytolytic function of c-Met+CD8+ T cells in cell-mediated cytotoxicity reactions CONCLUSIONS: Altogether, our findings suggest that the HGF/c-Met pathway could be exploited to modulate CD8+ T cell-mediated neuroinflammation.


CD8+ T cell; EAE; HGF; MS; Neuroinflammation; c-Met

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