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dc.contributor.authorZhou, Li
dc.contributor.authorWang, Hongjie
dc.contributor.authorZhong, Xing
dc.contributor.authorJin, Yulan
dc.contributor.authorMi, Qing-Sheng
dc.contributor.authorSharma, Ashok
dc.contributor.authorMcIndoe, Richard A
dc.contributor.authorGarge, Nikhil
dc.contributor.authorPodolsky, Robert H.
dc.contributor.authorShe, Jin-Xiong
dc.date.accessioned2010-09-24T20:59:18Z
dc.date.available2010-09-24T20:59:18Z
dc.date.issued2008-09-05en_US
dc.identifier.citationGenome Biol. 2008 Jul 29; 9(7):R119en_US
dc.identifier.issn1465-6914en_US
dc.identifier.pmid18664279en_US
dc.identifier.doi10.1186/gb-2008-9-7-r119en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/12
dc.description.abstractBACKGROUND: CD8+ NKT-like cells are naturally occurring but rare T cells that express both T cell and natural killer cell markers. These cells may play key roles in establishing tolerance to self-antigens; however, their mechanism of action and molecular profiles are poorly characterized due to their low frequencies. We developed an efficient in vitro protocol to produce CD8+ T cells that express natural killer cell markers (CD8+ NKT-like cells) and extensively characterized their functional and molecular phenotypes using a variety of techniques. RESULTS: Large numbers of CD8+ NKT-like cells were obtained through culture of na??ve CD8+ T cells using anti-CD3/anti-CD28-coated beads and high dose IL-2. These cells possess potent activity in suppressing the proliferation of na??ve responder T cells. Gene expression profiling suggests that the cultured CD8+ NKT-like cells and the na??ve CD8+ T cells differ by more than 2-fold for about 3,000 genes, among which 314 are upregulated by more than 5-fold and 113 are upregulated by more than 10-fold in the CD8+ NKT-like cells. A large proportion of the highly upregulated genes are soluble factors or surface markers that have previously been implicated in immune suppression or are likely to possess immunosuppressive properties. Many of these genes are regulated by two key cytokines, IL-10 and IFN-gamma. The immunosuppressive activities of cells cultured from IL-10-/- and IFN-gamma-/- mice are reduced by about 70% and about 50%, respectively, compared to wild-type mice. CONCLUSION: Immunosuppressive CD8+ NKT-like cells can be efficiently produced and their immunosuppressive activity is related to many surface and soluble molecules regulated by IL-10 and IFN-gamma.
dc.rightsThe PMC Open Access Subset is a relatively small part of the total collection of articles in PMC. Articles in the PMC Open Access Subset are still protected by copyright, but are made available under a Creative Commons or similar license that generally allows more liberal redistribution and reuse than a traditional copyrighted work. Please refer to the license statement in each article for specific terms of use. The license terms are not identical for all articles in this subset.en_US
dc.subject.meshAnimalsen_US
dc.subject.meshCD8-Positive T-Lymphocytes / classification / immunologyen_US
dc.subject.meshCells, Cultureden_US
dc.subject.meshGene Expression Profilingen_US
dc.subject.meshGene Expression Regulationen_US
dc.subject.meshImmune Toleranceen_US
dc.subject.meshInterferon-gamma / genetics / physiologyen_US
dc.subject.meshInterleukin-10 / genetics / physiologyen_US
dc.subject.meshKiller Cells, Natural / immunologyen_US
dc.subject.meshMembrane Proteins / biosynthesis / geneticsen_US
dc.subject.meshMiceen_US
dc.subject.meshMice, Knockouten_US
dc.subject.meshSuppressor Factors, Immunologic / biosynthesis / geneticsen_US
dc.subject.meshT-Lymphocyte Subsets / immunologyen_US
dc.subject.meshT-Lymphocytes, Regulatory / immunologyen_US
dc.subject.meshTranscription Factors / genetics / metabolismen_US
dc.titleThe IL-10 and IFN-gamma pathways are essential to the potent immunosuppressive activity of cultured CD8+ NKT-like cells.en_US
dc.typeJournal Articleen_US
dc.typeResearch Support, N.I.H., Extramuralen_US
dc.identifier.pmcidPMC2530876en_US
dc.contributor.corporatenameCenter for Biotechnology and Genomic Medicineen_US
dc.contributor.corporatenameDepartment of Pathologyen_US
dc.contributor.corporatenameDepartment of Medicineen_US
refterms.dateFOA2019-04-09T16:24:25Z
html.description.abstractBACKGROUND: CD8+ NKT-like cells are naturally occurring but rare T cells that express both T cell and natural killer cell markers. These cells may play key roles in establishing tolerance to self-antigens; however, their mechanism of action and molecular profiles are poorly characterized due to their low frequencies. We developed an efficient in vitro protocol to produce CD8+ T cells that express natural killer cell markers (CD8+ NKT-like cells) and extensively characterized their functional and molecular phenotypes using a variety of techniques. RESULTS: Large numbers of CD8+ NKT-like cells were obtained through culture of na??ve CD8+ T cells using anti-CD3/anti-CD28-coated beads and high dose IL-2. These cells possess potent activity in suppressing the proliferation of na??ve responder T cells. Gene expression profiling suggests that the cultured CD8+ NKT-like cells and the na??ve CD8+ T cells differ by more than 2-fold for about 3,000 genes, among which 314 are upregulated by more than 5-fold and 113 are upregulated by more than 10-fold in the CD8+ NKT-like cells. A large proportion of the highly upregulated genes are soluble factors or surface markers that have previously been implicated in immune suppression or are likely to possess immunosuppressive properties. Many of these genes are regulated by two key cytokines, IL-10 and IFN-gamma. The immunosuppressive activities of cells cultured from IL-10-/- and IFN-gamma-/- mice are reduced by about 70% and about 50%, respectively, compared to wild-type mice. CONCLUSION: Immunosuppressive CD8+ NKT-like cells can be efficiently produced and their immunosuppressive activity is related to many surface and soluble molecules regulated by IL-10 and IFN-gamma.


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