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

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Date: Feb. 19, 2020
From: Journal of Neuroinflammation(Vol. 17, Issue 1)
Publisher: BioMed Central Ltd.
Document Type: Report
Length: 6,403 words
Lexile Measure: 1530L

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Abstract :

Background CD8.sup.+ 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.sup.+ 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.sup.+ T cells by using a MOG.sub.35-55 T cell-mediated EAE model. Methods Mice were subcutaneously immunized with myelin oligodendrocyte glycoprotein peptide (MOG).sub.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. Results In the present study, we observed that a fraction of murine effector CD8.sup.+ T cells expressed c-Met receptor (c-Met.sup.+CD8.sup.+) in an experimental autoimmune encephalitis (EAE) model. Phenotypic and functional analysis of c-Met.sup.+CD8.sup.+ T cells revealed that they recognize the encephalitogenic epitope myelin oligodendrocyte glycoprotein.sub.37-50. We demonstrated that this T cell population produces higher levels of interferon-[gamma] and granzyme B ex vivo and that HGF directly restrains the cytolytic function of c-Met.sup.+CD8.sup.+ T cells in cell-mediated cytotoxicity reactions Conclusions Altogether, our findings suggest that the HGF/c-Met pathway could be exploited to modulate CD8.sup.+ T cell-mediated neuroinflammation. Keywords: HGF, c-Met, CD8.sup.+ T cell, Neuroinflammation, EAE, MS

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Gale Document Number: GALE|A616410658