CD4+NKG2D+ T cells exhibit enhanced migratory and encephalitogenic properties in neuroinflammation.
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 fo...
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2013
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oai:doaj.org-article:c8ebb82be39e4f35b7810c9fc93cb3c92021-11-18T08:44:48ZCD4+NKG2D+ T cells exhibit enhanced migratory and encephalitogenic properties in neuroinflammation.1932-620310.1371/journal.pone.0081455https://doaj.org/article/c8ebb82be39e4f35b7810c9fc93cb3c92013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24282598/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Migration 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.Tobias RuckStefan BittnerCatharina C GrossJohanna BreuerStefanie AlbrechtSabrina KorrKerstin GöbelSusann PankratzChristian M HenschelNicholas SchwabOri StaszewskiMarco PrinzTanja KuhlmannSven G MeuthHeinz WiendlPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 11, p e81455 (2013) |
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DOAJ |
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DOAJ |
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Medicine R Science Q |
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Medicine R Science Q Tobias Ruck Stefan Bittner Catharina C Gross Johanna Breuer Stefanie Albrecht Sabrina Korr Kerstin Göbel Susann Pankratz Christian M Henschel Nicholas Schwab Ori Staszewski Marco Prinz Tanja Kuhlmann Sven G Meuth Heinz Wiendl CD4+NKG2D+ T cells exhibit enhanced migratory and encephalitogenic properties in neuroinflammation. |
| description |
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. |
| format |
article |
| author |
Tobias Ruck Stefan Bittner Catharina C Gross Johanna Breuer Stefanie Albrecht Sabrina Korr Kerstin Göbel Susann Pankratz Christian M Henschel Nicholas Schwab Ori Staszewski Marco Prinz Tanja Kuhlmann Sven G Meuth Heinz Wiendl |
| author_facet |
Tobias Ruck Stefan Bittner Catharina C Gross Johanna Breuer Stefanie Albrecht Sabrina Korr Kerstin Göbel Susann Pankratz Christian M Henschel Nicholas Schwab Ori Staszewski Marco Prinz Tanja Kuhlmann Sven G Meuth Heinz Wiendl |
| author_sort |
Tobias Ruck |
| title |
CD4+NKG2D+ T cells exhibit enhanced migratory and encephalitogenic properties in neuroinflammation. |
| title_short |
CD4+NKG2D+ T cells exhibit enhanced migratory and encephalitogenic properties in neuroinflammation. |
| title_full |
CD4+NKG2D+ T cells exhibit enhanced migratory and encephalitogenic properties in neuroinflammation. |
| title_fullStr |
CD4+NKG2D+ T cells exhibit enhanced migratory and encephalitogenic properties in neuroinflammation. |
| title_full_unstemmed |
CD4+NKG2D+ T cells exhibit enhanced migratory and encephalitogenic properties in neuroinflammation. |
| title_sort |
cd4+nkg2d+ t cells exhibit enhanced migratory and encephalitogenic properties in neuroinflammation. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2013 |
| url |
https://doaj.org/article/c8ebb82be39e4f35b7810c9fc93cb3c9 |
| work_keys_str_mv |
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