Source:http://linkedlifedata.com/resource/pubmed/id/21577142
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
5
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| pubmed:dateCreated |
2011-5-19
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| pubmed:abstractText |
N-linked protein glycosylation represents an important cellular process for modifying protein properties. It resembles a cascade of various enzymatic reactions, in which class I ?-mannosidases play a central role. We and others have recently shown that N-glycosylation plays a major role for immune functions. We now analyzed the expression and function of ?-mannosidase I in CD4(+) naive and memory T cells studying human and murine T cells. Alpha-mannosidase I function was altered by (i) treatment with Kifunensine, a specific inhibitor class I ?-mannosidases, (ii) synthetic inhibitory RNA, and (iii) overexpression by retroviral gene transfer. T-cell activation was evaluated by CD69 expression, cytokine production and proliferation. Our results demonstrate (i) that ?-mannosidase I transcription is transiently downregulated after T-cell activation with either polyclonal anti-CD3/CD28 antibodies or allogeneic CD19(+) B cells, and (ii) that ?-mannosidase I exerts an inhibitory effect on T-cell activation. It is interesting to note that the inhibitory effect was restricted to naive CD4(+) T cells in both systems, human T cells and murine transgenic CD4(+)OT-II cells, whereas human memory T cells and primed CD4(+)OT-II cells remained unaffected. Alpha-mannosidase I inhibition reduced the activation threshold for naive but not already primed CD4(+)OT-II cells as the cells were able to respond to lower ovalbumin peptide concentrations and increased the rejection potential of alloreactive T cells in vivo. Thus, complex N-glycans generated by enzymes such as ?-mannosidase I inhibit the activation of naive T cells. These findings could be used to improve the ex vivo priming of naive T cells for adaptive T-cell therapies.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Alkaloids,
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/alpha-Mannosidase,
http://linkedlifedata.com/resource/pubmed/chemical/kifunensine
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| pubmed:status |
MEDLINE
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| pubmed:month |
Jun
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| pubmed:issn |
1537-4513
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| pubmed:author |
pubmed-author:AppeltChristineC,
pubmed-author:BrandtChristineC,
pubmed-author:GebuhrIngaI,
pubmed-author:HöflichConnyC,
pubmed-author:KeerenKathrinK,
pubmed-author:MeiselChristianC,
pubmed-author:SawitzkiBirgitB,
pubmed-author:SchlieerUlrikeU,
pubmed-author:VogtKatrinK,
pubmed-author:VolkHans-DieterHD
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| pubmed:issnType |
Electronic
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| pubmed:volume |
34
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
428-37
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| pubmed:meshHeading |
pubmed-meshheading:21577142-Alkaloids,
pubmed-meshheading:21577142-Animals,
pubmed-meshheading:21577142-Antibodies,
pubmed-meshheading:21577142-Antigens, CD,
pubmed-meshheading:21577142-B-Lymphocytes,
pubmed-meshheading:21577142-CD4-Positive T-Lymphocytes,
pubmed-meshheading:21577142-Enzyme Inhibitors,
pubmed-meshheading:21577142-Gene Silencing,
pubmed-meshheading:21577142-Humans,
pubmed-meshheading:21577142-Immunologic Memory,
pubmed-meshheading:21577142-Lymphocyte Activation,
pubmed-meshheading:21577142-Mice,
pubmed-meshheading:21577142-Mice, Inbred BALB C,
pubmed-meshheading:21577142-Mice, Inbred C57BL,
pubmed-meshheading:21577142-Mice, Transgenic,
pubmed-meshheading:21577142-RNA, Small Interfering,
pubmed-meshheading:21577142-Retroviridae,
pubmed-meshheading:21577142-Transcription, Genetic,
pubmed-meshheading:21577142-Transfection,
pubmed-meshheading:21577142-alpha-Mannosidase
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| pubmed:year |
2011
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| pubmed:articleTitle |
Differential expression and function of ?-mannosidase I in stimulated naive and memory CD4+ T cells.
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| pubmed:affiliation |
Institute of Medical Immunology, Charité-Universitätsmedizin, Berlin, Germany.
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| pubmed:publicationType |
Journal Article
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