CD20+inflammatory T-cells are present in blood and brain of multiple sclerosis patients and can be selectively targeted for apoptotic elimination

2.50
Hdl Handle:
http://hdl.handle.net/11287/593774
Title:
CD20+inflammatory T-cells are present in blood and brain of multiple sclerosis patients and can be selectively targeted for apoptotic elimination
Authors:
Holley, J. E.; Bremer, E.; Kendall, A. C.; de Bruyn, M.; Helfrich, W.; Tarr, J. M.; Newcombe, J.; Gutowski, Nicholas J.; Eggleton, Paul
Abstract:
BACKGROUND: A subset of T-cells expresses the B-cell marker CD20 and in rheumatoid arthritis secretes Interleukin (IL)-17. IL-17 secreting T-cells (Th17) have also been implicated in the inflammatory response in the central nervous system in multiple sclerosis (MS) and may be a potential target for elimination by biologic therapeutics. ScFvRit:sFasL comprises of a rituximab-derived antibody fragment scFvRit genetically fused to human soluble FasL that specifically eliminated T-cells. OBJECTIVE: To determine the presence and phenotype of CD20+T-cells in blood and brain of MS patients. Second, to determine whether scFvRit:sFasL can selectively eliminate CD20+T-cells. After CD20-selective binding, scFvRit:sFasL is designed to trigger FasL-mediated activation-induced cell death of T-cells, but not B-cells. METHODS: Flow cytometry and immunohistochemistry were used to screen for CD20+inflammatory T-cells in MS blood and brain tissue. ScFvRit:sFasL pro-apoptotic activity was evaluated by Annexin-V/PI staining followed by flow cytometry assessment. RESULTS: Peripheral blood (n=11) and chronic but not active lesions of MS patient brains (n=5) contained CD20+inflammatory T-cells. Activated CD20+T-cells were predominantly CD4+and secreted both IL-17 and INF-gamma. ScFvRit:sFasL triggered CD20-restricted FasL-mediated activation-induced cell death in peripheral blood CD20+T-cells, but not CD20+B-cells. CONCLUSION: CD20+inflammatory T-cells are present in blood and chronic brain lesions of MS patients. ScFvRit:sFasL selectively eliminated CD20+T-cells and may eliminate pathogenic T-cells without B-cell depletion.
Citation:
Mult Scler Relat Disord. 2014 Sep;3(5):650-8.
Publisher:
Elsevier
Journal:
Multiple sclerosis and related disorders
Issue Date:
1-Sep-2014
URI:
http://hdl.handle.net/11287/593774
DOI:
10.1016/j.msard.2014.06.001
PubMed ID:
26265276
Additional Links:
http://www.sciencedirect.com/science/article/pii/S2211034814000613
Type:
Journal Article; Research Support, Non-U.S. Gov't
Language:
eng
ISSN:
2211-0356
Appears in Collections:
Neurology; 2014 RD&E publications; Honorary contracts publications

Full metadata record

DC FieldValue Language
dc.contributor.authorHolley, J. E.en
dc.contributor.authorBremer, E.en
dc.contributor.authorKendall, A. C.en
dc.contributor.authorde Bruyn, M.en
dc.contributor.authorHelfrich, W.en
dc.contributor.authorTarr, J. M.en
dc.contributor.authorNewcombe, J.en
dc.contributor.authorGutowski, Nicholas J.en
dc.contributor.authorEggleton, Paulen
dc.date.accessioned2016-01-19T12:34:29Zen
dc.date.available2016-01-19T12:34:29Zen
dc.date.issued2014-09-01en
dc.identifier.citationMult Scler Relat Disord. 2014 Sep;3(5):650-8.en
dc.identifier.issn2211-0356en
dc.identifier.pmid26265276en
dc.identifier.doi10.1016/j.msard.2014.06.001en
dc.identifier.urihttp://hdl.handle.net/11287/593774en
dc.description.abstractBACKGROUND: A subset of T-cells expresses the B-cell marker CD20 and in rheumatoid arthritis secretes Interleukin (IL)-17. IL-17 secreting T-cells (Th17) have also been implicated in the inflammatory response in the central nervous system in multiple sclerosis (MS) and may be a potential target for elimination by biologic therapeutics. ScFvRit:sFasL comprises of a rituximab-derived antibody fragment scFvRit genetically fused to human soluble FasL that specifically eliminated T-cells. OBJECTIVE: To determine the presence and phenotype of CD20+T-cells in blood and brain of MS patients. Second, to determine whether scFvRit:sFasL can selectively eliminate CD20+T-cells. After CD20-selective binding, scFvRit:sFasL is designed to trigger FasL-mediated activation-induced cell death of T-cells, but not B-cells. METHODS: Flow cytometry and immunohistochemistry were used to screen for CD20+inflammatory T-cells in MS blood and brain tissue. ScFvRit:sFasL pro-apoptotic activity was evaluated by Annexin-V/PI staining followed by flow cytometry assessment. RESULTS: Peripheral blood (n=11) and chronic but not active lesions of MS patient brains (n=5) contained CD20+inflammatory T-cells. Activated CD20+T-cells were predominantly CD4+and secreted both IL-17 and INF-gamma. ScFvRit:sFasL triggered CD20-restricted FasL-mediated activation-induced cell death in peripheral blood CD20+T-cells, but not CD20+B-cells. CONCLUSION: CD20+inflammatory T-cells are present in blood and chronic brain lesions of MS patients. ScFvRit:sFasL selectively eliminated CD20+T-cells and may eliminate pathogenic T-cells without B-cell depletion.en
dc.language.isoengen
dc.publisherElsevieren
dc.relation.urlhttp://www.sciencedirect.com/science/article/pii/S2211034814000613en
dc.titleCD20+inflammatory T-cells are present in blood and brain of multiple sclerosis patients and can be selectively targeted for apoptotic eliminationen
dc.typeJournal Articleen
dc.typeResearch Support, Non-U.S. Gov'ten
dc.identifier.journalMultiple sclerosis and related disordersen

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