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

BACKGROUND: 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 MOG(35–55) T cell-mediated EAE model. METHODS: 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. RESULTS: 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 glycoprotein(37–50). 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.