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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.
- 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