A multidrug-resistance protein (MRP)-like transmembrane pump is highly expressed by resting murine T helper (Th) 2, but not Th1 cells, and is induced to equal expression levels in Th1 and Th2 cells after antigenic stimulation in vivo
A transmembrane pump for organic anions was identified in resting murine T helper (Th) 2, but not Th1 lymphocyte cell clones, as revealed by extrusion of a fluorescent dye. Dye extrusion inhibition studies suggested that the pump may be the multidrug-resistance protein (MRP). The different expressio...
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Veröffentlicht in: | The Journal of clinical investigation 1998-02, Vol.101 (3), p.703-710 |
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creator | Lohoff, M Prechtl, S Sommer, F Roellinghoff, M Schmitt, E Gradehandt, G Rohwer, P Stride, B D Cole, S P Deeley, R G |
description | A transmembrane pump for organic anions was identified in resting murine T helper (Th) 2, but not Th1 lymphocyte cell clones, as revealed by extrusion of a fluorescent dye. Dye extrusion inhibition studies suggested that the pump may be the multidrug-resistance protein (MRP). The different expression of the pump in resting Th1 and Th2 cell clones correlated with their respective levels of MRP mRNA. The pump was inducible in Th1 cells by antigenic stimulation in vitro leading to equal expression in activated Th1 and Th2 cell clones. This suggested that dye extrusion might allow the detection of Th2 (resting or activated) or of activated Th1 cells ex vivo based on a functional parameter. To test this, mice were infected with Leishmania major parasites to activate L. major-specific T cells of either Th1 (C57BL/6 mice) or Th2 (BALB/c mice) phenotype: 2-3% of CD4+ lymph node T cells of both strains of mice extruded the dye, defining a cell subset that did not coincide with subsets defined by other activation markers. Fluorescence-activated cell-sorting revealed that the lymphokine response (Th1 or Th2, respectively) to L. major antigens was restricted to this dye-extruding subset. |
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Dye extrusion inhibition studies suggested that the pump may be the multidrug-resistance protein (MRP). The different expression of the pump in resting Th1 and Th2 cell clones correlated with their respective levels of MRP mRNA. The pump was inducible in Th1 cells by antigenic stimulation in vitro leading to equal expression in activated Th1 and Th2 cell clones. This suggested that dye extrusion might allow the detection of Th2 (resting or activated) or of activated Th1 cells ex vivo based on a functional parameter. To test this, mice were infected with Leishmania major parasites to activate L. major-specific T cells of either Th1 (C57BL/6 mice) or Th2 (BALB/c mice) phenotype: 2-3% of CD4+ lymph node T cells of both strains of mice extruded the dye, defining a cell subset that did not coincide with subsets defined by other activation markers. Fluorescence-activated cell-sorting revealed that the lymphokine response (Th1 or Th2, respectively) to L. major antigens was restricted to this dye-extruding subset.</description><identifier>ISSN: 0021-9738</identifier><identifier>DOI: 10.1172/JCI824</identifier><identifier>PMID: 9449706</identifier><language>eng</language><publisher>United States</publisher><subject>AIDS/HIV ; Aniline Compounds - metabolism ; Animals ; Antigens, Protozoan - immunology ; ATP-Binding Cassette, Sub-Family B, Member 1 - biosynthesis ; ATP-Binding Cassette, Sub-Family B, Member 1 - genetics ; CD4-Positive T-Lymphocytes - cytology ; CD4-Positive T-Lymphocytes - immunology ; CD4-Positive T-Lymphocytes - metabolism ; Cell Line ; Clone Cells ; Drug Resistance, Multiple ; Fluorescent Dyes - metabolism ; Ion Pumps - biosynthesis ; Ion Pumps - genetics ; Leishmania major - immunology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Th1 Cells - cytology ; Th1 Cells - immunology ; Th1 Cells - metabolism ; Th2 Cells - cytology ; Th2 Cells - immunology ; Th2 Cells - metabolism ; Xanthenes - metabolism</subject><ispartof>The Journal of clinical investigation, 1998-02, Vol.101 (3), p.703-710</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c391t-9f5007507db42921b6dead89fe76d56f7e5b3253dbea41f1a2dd8063737c46613</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC508616/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC508616/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,725,778,782,883,27907,27908,53774,53776</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9449706$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lohoff, M</creatorcontrib><creatorcontrib>Prechtl, S</creatorcontrib><creatorcontrib>Sommer, F</creatorcontrib><creatorcontrib>Roellinghoff, M</creatorcontrib><creatorcontrib>Schmitt, E</creatorcontrib><creatorcontrib>Gradehandt, G</creatorcontrib><creatorcontrib>Rohwer, P</creatorcontrib><creatorcontrib>Stride, B D</creatorcontrib><creatorcontrib>Cole, S P</creatorcontrib><creatorcontrib>Deeley, R G</creatorcontrib><title>A multidrug-resistance protein (MRP)-like transmembrane pump is highly expressed by resting murine T helper (Th) 2, but not Th1 cells, and is induced to equal expression levels in Th1 and Th2 cells after antigenic stimulation in vivo</title><title>The Journal of clinical investigation</title><addtitle>J Clin Invest</addtitle><description>A transmembrane pump for organic anions was identified in resting murine T helper (Th) 2, but not Th1 lymphocyte cell clones, as revealed by extrusion of a fluorescent dye. Dye extrusion inhibition studies suggested that the pump may be the multidrug-resistance protein (MRP). The different expression of the pump in resting Th1 and Th2 cell clones correlated with their respective levels of MRP mRNA. The pump was inducible in Th1 cells by antigenic stimulation in vitro leading to equal expression in activated Th1 and Th2 cell clones. This suggested that dye extrusion might allow the detection of Th2 (resting or activated) or of activated Th1 cells ex vivo based on a functional parameter. To test this, mice were infected with Leishmania major parasites to activate L. major-specific T cells of either Th1 (C57BL/6 mice) or Th2 (BALB/c mice) phenotype: 2-3% of CD4+ lymph node T cells of both strains of mice extruded the dye, defining a cell subset that did not coincide with subsets defined by other activation markers. Fluorescence-activated cell-sorting revealed that the lymphokine response (Th1 or Th2, respectively) to L. major antigens was restricted to this dye-extruding subset.</description><subject>AIDS/HIV</subject><subject>Aniline Compounds - metabolism</subject><subject>Animals</subject><subject>Antigens, Protozoan - immunology</subject><subject>ATP-Binding Cassette, Sub-Family B, Member 1 - biosynthesis</subject><subject>ATP-Binding Cassette, Sub-Family B, Member 1 - genetics</subject><subject>CD4-Positive T-Lymphocytes - cytology</subject><subject>CD4-Positive T-Lymphocytes - immunology</subject><subject>CD4-Positive T-Lymphocytes - metabolism</subject><subject>Cell Line</subject><subject>Clone Cells</subject><subject>Drug Resistance, Multiple</subject><subject>Fluorescent Dyes - metabolism</subject><subject>Ion Pumps - biosynthesis</subject><subject>Ion Pumps - genetics</subject><subject>Leishmania major - immunology</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Inbred C57BL</subject><subject>Th1 Cells - cytology</subject><subject>Th1 Cells - immunology</subject><subject>Th1 Cells - metabolism</subject><subject>Th2 Cells - cytology</subject><subject>Th2 Cells - immunology</subject><subject>Th2 Cells - metabolism</subject><subject>Xanthenes - metabolism</subject><issn>0021-9738</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkstu1DAUhrMAlVLgDZDOCrVSA7aT2MmCRTXiUlQEQmEdOfHJxOA4qe2MmEfmLXCYYQQrVudI_r_f55Ykzyh5Salgrz5sbkuWP0jOCWE0rURWPkoee_-NEJrnRX6WnFV5XgnCz5OfNzAuJmjllm3q0GsfpO0QZjcF1BYuP375fJUa_R0hOGn9iGMbYxQs4wzaw6C3g9kD_pgj7VFBu4eYBW230dnpKK1hQDOjg8t6uAJ2De0SwE4B6oFCh8b4a5BWrW7aqqWLJmECvF-k-eOrJwsGd2hWyW9uBeqBHXiQfYj-0ga9Ras7iP_HtmRYuQjs9G56kjzspfH49Bgvkq9v39Sb9-ndp3e3m5u7tMsqGtKqLwgRBRGqzVnFaMsVSlVWPQquCt4LLNqMFZlqUea0p5IpVRKeiUx0Oec0u0heH3znpR1RdWjj4EwzOz1Kt28mqZt_X6wemu20awpScsoj_-LIu-l-iZNsRu3XLuPUp8U3ouJxoSz7r5DynNEsbv8k7NzkvcP-VAwlzXowzeFgovD536WfZMdryX4BJQvBTA</recordid><startdate>19980201</startdate><enddate>19980201</enddate><creator>Lohoff, M</creator><creator>Prechtl, S</creator><creator>Sommer, F</creator><creator>Roellinghoff, M</creator><creator>Schmitt, E</creator><creator>Gradehandt, G</creator><creator>Rohwer, P</creator><creator>Stride, B D</creator><creator>Cole, S P</creator><creator>Deeley, R G</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>H94</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>19980201</creationdate><title>A multidrug-resistance protein (MRP)-like transmembrane pump is highly expressed by resting murine T helper (Th) 2, but not Th1 cells, and is induced to equal expression levels in Th1 and Th2 cells after antigenic stimulation in vivo</title><author>Lohoff, M ; Prechtl, S ; Sommer, F ; Roellinghoff, M ; Schmitt, E ; Gradehandt, G ; Rohwer, P ; Stride, B D ; Cole, S P ; Deeley, R G</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c391t-9f5007507db42921b6dead89fe76d56f7e5b3253dbea41f1a2dd8063737c46613</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1998</creationdate><topic>AIDS/HIV</topic><topic>Aniline Compounds - metabolism</topic><topic>Animals</topic><topic>Antigens, Protozoan - immunology</topic><topic>ATP-Binding Cassette, Sub-Family B, Member 1 - biosynthesis</topic><topic>ATP-Binding Cassette, Sub-Family B, Member 1 - genetics</topic><topic>CD4-Positive T-Lymphocytes - cytology</topic><topic>CD4-Positive T-Lymphocytes - immunology</topic><topic>CD4-Positive T-Lymphocytes - metabolism</topic><topic>Cell Line</topic><topic>Clone Cells</topic><topic>Drug Resistance, Multiple</topic><topic>Fluorescent Dyes - metabolism</topic><topic>Ion Pumps - biosynthesis</topic><topic>Ion Pumps - genetics</topic><topic>Leishmania major - immunology</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Inbred C57BL</topic><topic>Th1 Cells - cytology</topic><topic>Th1 Cells - immunology</topic><topic>Th1 Cells - metabolism</topic><topic>Th2 Cells - cytology</topic><topic>Th2 Cells - immunology</topic><topic>Th2 Cells - metabolism</topic><topic>Xanthenes - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lohoff, M</creatorcontrib><creatorcontrib>Prechtl, S</creatorcontrib><creatorcontrib>Sommer, F</creatorcontrib><creatorcontrib>Roellinghoff, M</creatorcontrib><creatorcontrib>Schmitt, E</creatorcontrib><creatorcontrib>Gradehandt, G</creatorcontrib><creatorcontrib>Rohwer, P</creatorcontrib><creatorcontrib>Stride, B D</creatorcontrib><creatorcontrib>Cole, S P</creatorcontrib><creatorcontrib>Deeley, R G</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of clinical investigation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lohoff, M</au><au>Prechtl, S</au><au>Sommer, F</au><au>Roellinghoff, M</au><au>Schmitt, E</au><au>Gradehandt, G</au><au>Rohwer, P</au><au>Stride, B D</au><au>Cole, S P</au><au>Deeley, R G</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A multidrug-resistance protein (MRP)-like transmembrane pump is highly expressed by resting murine T helper (Th) 2, but not Th1 cells, and is induced to equal expression levels in Th1 and Th2 cells after antigenic stimulation in vivo</atitle><jtitle>The Journal of clinical investigation</jtitle><addtitle>J Clin Invest</addtitle><date>1998-02-01</date><risdate>1998</risdate><volume>101</volume><issue>3</issue><spage>703</spage><epage>710</epage><pages>703-710</pages><issn>0021-9738</issn><abstract>A transmembrane pump for organic anions was identified in resting murine T helper (Th) 2, but not Th1 lymphocyte cell clones, as revealed by extrusion of a fluorescent dye. Dye extrusion inhibition studies suggested that the pump may be the multidrug-resistance protein (MRP). The different expression of the pump in resting Th1 and Th2 cell clones correlated with their respective levels of MRP mRNA. The pump was inducible in Th1 cells by antigenic stimulation in vitro leading to equal expression in activated Th1 and Th2 cell clones. This suggested that dye extrusion might allow the detection of Th2 (resting or activated) or of activated Th1 cells ex vivo based on a functional parameter. To test this, mice were infected with Leishmania major parasites to activate L. major-specific T cells of either Th1 (C57BL/6 mice) or Th2 (BALB/c mice) phenotype: 2-3% of CD4+ lymph node T cells of both strains of mice extruded the dye, defining a cell subset that did not coincide with subsets defined by other activation markers. Fluorescence-activated cell-sorting revealed that the lymphokine response (Th1 or Th2, respectively) to L. major antigens was restricted to this dye-extruding subset.</abstract><cop>United States</cop><pmid>9449706</pmid><doi>10.1172/JCI824</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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subjects | AIDS/HIV Aniline Compounds - metabolism Animals Antigens, Protozoan - immunology ATP-Binding Cassette, Sub-Family B, Member 1 - biosynthesis ATP-Binding Cassette, Sub-Family B, Member 1 - genetics CD4-Positive T-Lymphocytes - cytology CD4-Positive T-Lymphocytes - immunology CD4-Positive T-Lymphocytes - metabolism Cell Line Clone Cells Drug Resistance, Multiple Fluorescent Dyes - metabolism Ion Pumps - biosynthesis Ion Pumps - genetics Leishmania major - immunology Mice Mice, Inbred BALB C Mice, Inbred C57BL Th1 Cells - cytology Th1 Cells - immunology Th1 Cells - metabolism Th2 Cells - cytology Th2 Cells - immunology Th2 Cells - metabolism Xanthenes - metabolism |
title | A multidrug-resistance protein (MRP)-like transmembrane pump is highly expressed by resting murine T helper (Th) 2, but not Th1 cells, and is induced to equal expression levels in Th1 and Th2 cells after antigenic stimulation in vivo |
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