Details

Autor(en) / Beteiligte

• Ruck, Tobias
• Bittner, Stefan
• Gross, Catharina C
• Breuer, Johanna
• Albrecht, Stefanie
• Korr, Sabrina
• Gobel, Kerstin
• Pankratz, Susann
• Henschel, Christian M
• Schwab, Nicholas

Titel

CD4+NKG2D+ T Cells Exhibit Enhanced Migratory and Encephalitogenic Properties in Neuroinflammation: e81455

Ist Teil von

• PloS one, 2013-11, Vol.8 (11)

Erscheinungsjahr

2013

Link zum Volltext

Quelle

Elektronische Zeitschriftenbibliothek (Open access)

Beschreibungen/Notizen

• 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- gamma 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.