/home/ikeda/eclipse/workspace/macrophage/csml/ok/csml/11090938.csml - 2009.07.01.10:39

Original Literature	Model OverView
Publication Title Induction of proliferation and cytokine production in human T lymphocytes bylipopolysaccharide (LPS). Authors Ulmer AJ, Flad H, Rietschel T, Mattern T. Affiliation Department of Immunology and Cell Biology, Division of Cellular Immunology,Research Center Borstel, Parkallee 22, 23845, Borstel, Germany.ajulmer@fz-borstel.de Abstract Lipopolysaccharide (LPS), also known as endotoxin, is a compound of the cellwall of Gram-negative bacteria, which has been demonstrated to induceinflammatory reactions in vitro as well as in vivo, including lethal shock. Agreat number of different cells have been documented to be reactive to LPS, e.g.monocytes/macrophages, vascular cells, polymorphonuclear cells, and even Blymphocytes. We have now established that T lymphocytes could also contribute toan inflammatory reaction to LPS. LPS is a potent inducer of human T-lymphocyteproliferation and cytokine production. The activation of T lymphocytes by LPSrequires direct cell-to-cell contact with viable accessory monocytes. Thisinteraction was found to be MHC-unrestricted, but strongly dependent oncostimulatory signals provided by B7/CD28 interactions. The frequency ofresponding T lymphocytes is less than 1:1000. A very exciting finding was thatnot only monocytes, but also CD34+ hematopoietic stem cells, which circulate inperipheral blood in very low frequency, exert essential accessory cell activityduring stimulation of T lymphocytes by LPS. In contrast, the response of Tlymphocytes to conventional recall antigens is not controlled by blood stemcells. These conclusions are based on the observation that depletion ofCD34-positive blood stem cells resulted in a complete loss of LPS-inducedT-lymphocyte stimulation. Addition of CD34-enriched blood stem cells led to arecovery of reactivity of T lymphocyte to LPS. The characteristics ofT-lymphocyte activation indicate that LPS is neither active as a mitogen, or asa superantigen, or as a classical antigen, but may activate T lymphocyte througha new, so far undescribed, mechanism. Furthermore, the involvement ofhematopoietic blood stem cells in the activation of T lymphocytes by LPSdemonstrates a role of these cells in inflammatory and immunological events. PMID 11090938

Model Detail

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B7: CD28

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LPS: Unknowm Receptor: TCR

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LPS: Unknown Receptor

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389.0, 208.0

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349.5, 932.0

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345.5, 996.0

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326.0883925363628, 869.1262283325384

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330.42127827524484, 872.9131076014799

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326.0883925363628, 869.1262283325384

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219.90642141736046, 454.5400666187362

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226.77701954859006, 478.9959918883706

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269.0, 285.0

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cso30:i:ME_Binding

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mass

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PMID: 11090938, 8717514, 7516408 Interaction of CD28 on T lymphocytes with their ligands B7.1 and B7.2 (CD80 and CD86) on monocytes are known to deliver such ostimulatory signals. We therefore investigated the role of these costimulatory signals during LPS-induced T-lymphocyte proliferation using soluble CTLA-4Ig, which blocks B7:CD28 interactions.

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589.0, 229.0

30.0, 30.0

cso30:i:ME_Binding

cso30:i:CC_Extracellular

e14 e16

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mass

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PMID: 11090938 We found that these LPS-pulsed monocytes could stimulate human T lymphocytes, suggesting that one function of accessory monocytes during activation of T lymphocytes by LPS was to present costimulatory signal(s).

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649.0, 325.0

30.0, 30.0

cso30:i:ME_Binding

cso30:i:CC_Extracellular

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PMID: 11090938 the interaction of LPSprimed monocytes with T cells was not MHC-restricted. This interaction was found to be MHC-unrestricted, but strongly dependent on costimulatory signals provided by B7:CD28 interactions. LPS-primed monocytes provide costimulatory signals through CD28 and/or CTLA-4/B7 interactions.

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441.0, 541.0

30.0, 30.0

cso30:i:ME_Binding

cso30:i:CC_Cytosol

e6 e20

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and

mass

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m6*m20*0.1

nodelay

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PMID:11090938 LPS-primed monocytes provide costimulatory signals through CD28 and/or CTLA-4/B7 interactions.

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457.0, 125.0

30.0, 30.0

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleolus

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PMID: 11090938 Human MNC, stimulated with LPS, not only expressed mRNA for the monokines interleukin (IL)-1, IL-6 and tumor necrosis factor-alpha (TNF-a), but also mRNA for the T helper 1 (Th1)-cytokines interferongamma (IFN-g) and IL-2.

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453.0, 173.0

30.0, 30.0

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleolus

e18

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m18*0.1

nodelay