title: CD4+NKG2D+ T cells exhibit enhanced migratory and encephalitogenic properties in neuroinflammation.
abstract: Migration of encephalitogenic CD4(+) T lymphocytes across the blood-brain barrier is an essential step in the pathogenesis of multiple sclerosis (MS). We here demonstrate that expression of the co-stimulatory receptor NKG2D defines a subpopulation of CD4(+) T cells with elevated levels of markers for migration, activation, and cytolytic capacity especially when derived from MS patients. Furthermore, CD4(+)NKG2D(+) cells produce high levels of proinflammatory IFN-γ and IL-17 upon stimulation. NKG2D promotes the capacity of CD4(+)NKG2D(+) cells to migrate across endothelial cells in an in vitro model of the blood-brain barrier. CD4(+)NKG2D(+) T cells are enriched in the cerebrospinal fluid of MS patients, and a significant number of CD4(+) T cells in MS lesions coexpress NKG2D. We further elucidated the role of CD4(+)NKG2D(+) T cells in the mouse system. NKG2D blockade restricted central nervous system migration of T lymphocytes in vivo, leading to a significant decrease in the clinical and pathologic severity of experimental autoimmune encephalomyelitis, an animal model of MS. Blockade of NKG2D reduced killing of cultivated mouse oligodendrocytes by activated CD4(+) T cells. Taken together, we identify CD4(+)NKG2D(+) cells as a subpopulation of T helper cells with enhanced migratory, encephalitogenic and cytotoxic properties involved in inflammatory CNS lesion development.
authors.affiliation: Department of Neurology, University of Münster, Münster, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Ruck
authors.forename: Stefan
authors.initials: S
authors.lastname: Bittner
authors.forename: Catharina C
authors.initials: CC
authors.lastname: Gross
authors.forename: Johanna
authors.initials: J
authors.lastname: Breuer
authors.forename: Stefanie
authors.initials: S
authors.lastname: Albrecht
authors.forename: Sabrina
authors.initials: S
authors.lastname: Korr
authors.forename: Kerstin
authors.initials: K
authors.lastname: Göbel
authors.forename: Susann
authors.initials: S
authors.lastname: Pankratz
authors.forename: Christian M
authors.initials: CM
authors.lastname: Henschel
authors.forename: Nicholas
authors.initials: N
authors.lastname: Schwab
authors.forename: Ori
authors.initials: O
authors.lastname: Staszewski
authors.forename: Marco
authors.initials: M
authors.lastname: Prinz
authors.forename: Tanja
authors.initials: T
authors.lastname: Kuhlmann
authors.forename: Sven G
authors.initials: SG
authors.lastname: Meuth
authors.forename: Heinz
authors.initials: H
authors.lastname: Wiendl
mesh_terms: D001812:Blood-Brain Barrier; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D002634:Chemotaxis, Leukocyte; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D009103:Multiple Sclerosis / Q000276:immunology / Q000473:pathology; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: C527085:KLRK1 protein, human; D055655:NK Cell Lectin-Like Receptor Subfamily K