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

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

Authors :
Ruck, Tobias
Bittner, Stefan
Gross, Catharina C.
Breuer, Johanna
Albrecht, Stefanie
Korr, Sabrina
Göbel, Kerstin
Pankratz, Susann
Henschel, Christian M.
Schwab, Nicholas
Staszewski, Ori
Prinz, Marco
Kuhlmann, Tanja
Meuth, Sven G.
Wiendl, Heinz
Source :
PLoS ONE; Nov2013, Vol. 8 Issue 11, p1-1, 1p
Publication Year :
2013

Abstract

Migration of encephalitogenic CD4<superscript>+</superscript> 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<superscript>+</superscript> T cells with elevated levels of markers for migration, activation, and cytolytic capacity especially when derived from MS patients. Furthermore, CD4<superscript>+</superscript>NKG2D<superscript>+</superscript> cells produce high levels of proinflammatory IFN-γ and IL-17 upon stimulation. NKG2D promotes the capacity of CD4<superscript>+</superscript>NKG2D<superscript>+</superscript> cells to migrate across endothelial cells in an in vitro model of the blood-brain barrier. CD4<superscript>+</superscript>NKG2D<superscript>+</superscript> T cells are enriched in the cerebrospinal fluid of MS patients, and a significant number of CD4<superscript>+</superscript> T cells in MS lesions coexpress NKG2D. We further elucidated the role of CD4<superscript>+</superscript>NKG2D<superscript>+</superscript> 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<superscript>+</superscript> T cells. Taken together, we identify CD4<superscript>+</superscript>NKG2D<superscript>+</superscript> cells as a subpopulation of T helper cells with enhanced migratory, encephalitogenic and cytotoxic properties involved in inflammatory CNS lesion development. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
19326203
Volume :
8
Issue :
11
Database :
Complementary Index
Journal :
PLoS ONE
Publication Type :
Academic Journal
Accession number :
92671224
Full Text :
https://doi.org/10.1371/journal.pone.0081455