Chemokine Receptor Expression and Function in CD4+ T Lymphocytes with Regulatory Activity
We have investigated the chemokine receptor expression and migratory behavior of a new subset of nickel-specific skin-homing regulatory CD4(+) T cells (Th(IL-10)) releasing high levels of IL-10, low IFN-gamma, and undetectable IL-4. These cells inhibit in a IL-10-dependent manner the capacity of den...
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Veröffentlicht in: | The Journal of immunology (1950) 2001-01, Vol.166 (2), p.996-1002 |
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description | We have investigated the chemokine receptor expression and migratory behavior of a new subset of nickel-specific skin-homing regulatory CD4(+) T cells (Th(IL-10)) releasing high levels of IL-10, low IFN-gamma, and undetectable IL-4. These cells inhibit in a IL-10-dependent manner the capacity of dendritic cells to activate nickel-specific Tc1 and Th1 lymphocytes. RNase protection assay and FACS analysis revealed the expression of a vast repertoire of chemokine receptors on resting Th(IL-10), including the Th1-associated CXCR3 and CCR5, and the Th2-associated CCR3, CCR4, and CCR8, the latter at higher levels compared with Th2 cells. The most active chemokines for resting Th(IL-10), in terms of calcium mobilization and in vitro migration, were in order of potency: CCL2 (monocyte chemoattractant protein-1, CCR2 ligand), CCL4 (macrophage-inflammatory protein-1beta, CCR5 ligand), CCL3 (macrophage-inflammatory protein-1alpha, CCR1/5 ligand), CCL17 (thymus and activation-regulated chemokine, CCR4 ligand), CCL1 (I-309, CCR8 ligand), CXCL12 (stromal-derived factor-1, CXCR4), and CCL11 (eotaxin, CCR3 ligand). Consistent with receptor expression down-regulation, activated Th(IL-10) exhibited a reduced or absent response to most chemokines, but retained a significant migratory capacity to I-309, monocyte chemoattractant protein-1, and thymus and activation-regulated chemokine. I-309, which was ineffective on Th1 lymphocytes, attracted more efficiently Th(IL-10) than Th2 cells. I-309 and CCR8 mRNAs were not detected in unaffected skin and were up-regulated at the skin site of nickel-allergic reaction, with an earlier expression kinetics compared with IL-10 and IL-4. Results indicate that skin-homing regulatory Th(IL-10) lymphocytes coexpress functional Th1- and Th2-associated chemokine receptors, and that CCR8/I-309-driven recruitment of both resting and activated Th(IL-10) cells may be critically involved in the regulation of Th1-mediated skin allergic disorders. |
doi_str_mv | 10.4049/jimmunol.166.2.996 |
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These cells inhibit in a IL-10-dependent manner the capacity of dendritic cells to activate nickel-specific Tc1 and Th1 lymphocytes. RNase protection assay and FACS analysis revealed the expression of a vast repertoire of chemokine receptors on resting Th(IL-10), including the Th1-associated CXCR3 and CCR5, and the Th2-associated CCR3, CCR4, and CCR8, the latter at higher levels compared with Th2 cells. The most active chemokines for resting Th(IL-10), in terms of calcium mobilization and in vitro migration, were in order of potency: CCL2 (monocyte chemoattractant protein-1, CCR2 ligand), CCL4 (macrophage-inflammatory protein-1beta, CCR5 ligand), CCL3 (macrophage-inflammatory protein-1alpha, CCR1/5 ligand), CCL17 (thymus and activation-regulated chemokine, CCR4 ligand), CCL1 (I-309, CCR8 ligand), CXCL12 (stromal-derived factor-1, CXCR4), and CCL11 (eotaxin, CCR3 ligand). Consistent with receptor expression down-regulation, activated Th(IL-10) exhibited a reduced or absent response to most chemokines, but retained a significant migratory capacity to I-309, monocyte chemoattractant protein-1, and thymus and activation-regulated chemokine. I-309, which was ineffective on Th1 lymphocytes, attracted more efficiently Th(IL-10) than Th2 cells. I-309 and CCR8 mRNAs were not detected in unaffected skin and were up-regulated at the skin site of nickel-allergic reaction, with an earlier expression kinetics compared with IL-10 and IL-4. Results indicate that skin-homing regulatory Th(IL-10) lymphocytes coexpress functional Th1- and Th2-associated chemokine receptors, and that CCR8/I-309-driven recruitment of both resting and activated Th(IL-10) cells may be critically involved in the regulation of Th1-mediated skin allergic disorders.</description><identifier>ISSN: 0022-1767</identifier><identifier>EISSN: 1550-6606</identifier><identifier>DOI: 10.4049/jimmunol.166.2.996</identifier><identifier>PMID: 11145678</identifier><language>eng</language><publisher>United States: Am Assoc Immnol</publisher><subject>CD4-Positive T-Lymphocytes - immunology ; CD4-Positive T-Lymphocytes - metabolism ; Cell Line ; Chemokine CCL1 ; Chemokines, CC - biosynthesis ; Chemokines, CC - genetics ; Chemokines, CC - metabolism ; Chemotaxis, Leukocyte - immunology ; Clone Cells ; Cytokines - biosynthesis ; Cytokines - genetics ; Dermatitis, Allergic Contact - immunology ; Epitopes, T-Lymphocyte - immunology ; Humans ; Interleukin-10 - biosynthesis ; Interleukin-10 - genetics ; Interphase - genetics ; Interphase - immunology ; Lymphocyte Activation - genetics ; Nickel - immunology ; Receptors, CCR8 ; Receptors, Chemokine - biosynthesis ; Receptors, Chemokine - genetics ; Receptors, Chemokine - physiology ; RNA, Messenger - analysis ; RNA, Messenger - biosynthesis ; Signal Transduction - immunology ; T-Lymphocyte Subsets - immunology ; T-Lymphocyte Subsets - metabolism ; Th1 Cells - immunology ; Th1 Cells - metabolism ; Th2 Cells - immunology ; Th2 Cells - metabolism</subject><ispartof>The Journal of immunology (1950), 2001-01, Vol.166 (2), p.996-1002</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c374t-866cb1bf4caf1d0764ddabc1ca252bc30101f94855226449aaa2d0398f04d2443</citedby><cites>FETCH-LOGICAL-c374t-866cb1bf4caf1d0764ddabc1ca252bc30101f94855226449aaa2d0398f04d2443</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27922,27923</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11145678$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sebastiani, Silvia</creatorcontrib><creatorcontrib>Allavena, Paola</creatorcontrib><creatorcontrib>Albanesi, Cristina</creatorcontrib><creatorcontrib>Nasorri, Francesca</creatorcontrib><creatorcontrib>Bianchi, Giancarlo</creatorcontrib><creatorcontrib>Traidl, Claudia</creatorcontrib><creatorcontrib>Sozzani, Silvano</creatorcontrib><creatorcontrib>Girolomoni, Giampiero</creatorcontrib><creatorcontrib>Cavani, Andrea</creatorcontrib><title>Chemokine Receptor Expression and Function in CD4+ T Lymphocytes with Regulatory Activity</title><title>The Journal of immunology (1950)</title><addtitle>J Immunol</addtitle><description>We have investigated the chemokine receptor expression and migratory behavior of a new subset of nickel-specific skin-homing regulatory CD4(+) T cells (Th(IL-10)) releasing high levels of IL-10, low IFN-gamma, and undetectable IL-4. These cells inhibit in a IL-10-dependent manner the capacity of dendritic cells to activate nickel-specific Tc1 and Th1 lymphocytes. RNase protection assay and FACS analysis revealed the expression of a vast repertoire of chemokine receptors on resting Th(IL-10), including the Th1-associated CXCR3 and CCR5, and the Th2-associated CCR3, CCR4, and CCR8, the latter at higher levels compared with Th2 cells. The most active chemokines for resting Th(IL-10), in terms of calcium mobilization and in vitro migration, were in order of potency: CCL2 (monocyte chemoattractant protein-1, CCR2 ligand), CCL4 (macrophage-inflammatory protein-1beta, CCR5 ligand), CCL3 (macrophage-inflammatory protein-1alpha, CCR1/5 ligand), CCL17 (thymus and activation-regulated chemokine, CCR4 ligand), CCL1 (I-309, CCR8 ligand), CXCL12 (stromal-derived factor-1, CXCR4), and CCL11 (eotaxin, CCR3 ligand). Consistent with receptor expression down-regulation, activated Th(IL-10) exhibited a reduced or absent response to most chemokines, but retained a significant migratory capacity to I-309, monocyte chemoattractant protein-1, and thymus and activation-regulated chemokine. I-309, which was ineffective on Th1 lymphocytes, attracted more efficiently Th(IL-10) than Th2 cells. I-309 and CCR8 mRNAs were not detected in unaffected skin and were up-regulated at the skin site of nickel-allergic reaction, with an earlier expression kinetics compared with IL-10 and IL-4. Results indicate that skin-homing regulatory Th(IL-10) lymphocytes coexpress functional Th1- and Th2-associated chemokine receptors, and that CCR8/I-309-driven recruitment of both resting and activated Th(IL-10) cells may be critically involved in the regulation of Th1-mediated skin allergic disorders.</description><subject>CD4-Positive T-Lymphocytes - immunology</subject><subject>CD4-Positive T-Lymphocytes - metabolism</subject><subject>Cell Line</subject><subject>Chemokine CCL1</subject><subject>Chemokines, CC - biosynthesis</subject><subject>Chemokines, CC - genetics</subject><subject>Chemokines, CC - metabolism</subject><subject>Chemotaxis, Leukocyte - immunology</subject><subject>Clone Cells</subject><subject>Cytokines - biosynthesis</subject><subject>Cytokines - genetics</subject><subject>Dermatitis, Allergic Contact - immunology</subject><subject>Epitopes, T-Lymphocyte - immunology</subject><subject>Humans</subject><subject>Interleukin-10 - biosynthesis</subject><subject>Interleukin-10 - genetics</subject><subject>Interphase - genetics</subject><subject>Interphase - immunology</subject><subject>Lymphocyte Activation - genetics</subject><subject>Nickel - immunology</subject><subject>Receptors, CCR8</subject><subject>Receptors, Chemokine - biosynthesis</subject><subject>Receptors, Chemokine - genetics</subject><subject>Receptors, Chemokine - physiology</subject><subject>RNA, Messenger - analysis</subject><subject>RNA, Messenger - biosynthesis</subject><subject>Signal Transduction - immunology</subject><subject>T-Lymphocyte Subsets - immunology</subject><subject>T-Lymphocyte Subsets - metabolism</subject><subject>Th1 Cells - immunology</subject><subject>Th1 Cells - metabolism</subject><subject>Th2 Cells - immunology</subject><subject>Th2 Cells - metabolism</subject><issn>0022-1767</issn><issn>1550-6606</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkE9LwzAYh4Mobk6_gAfJyYt0vknTdD2OuakwEGQePIU0TdfM_rNprf32ZmyyU3jheX6BB6FbAlMGLHrcmaLoyiqfEs6ndBpF_AyNSRCAxznwczQGoNQjIQ9H6MraHQBwoOwSjQghLODhbIw-F5kuqi9Tavyula7bqsHL37rR1pqqxLJM8KorVbs_TIkXT-wBb_B6KOqsUkOrLe5Nmzl32-XSyQOeO_jHtMM1ukhlbvXN8Z2gj9Vys3jx1m_Pr4v52lN-yFpvxrmKSZwyJVOSQMhZkshYESVpQGPlAwGSRmwWBJRyxiIpJU3Aj2YpsIQy5k_Q_WG3bqrvTttWFMYqneey1FVnRQiBK0DAgfQAqqayttGpqBtTyGYQBMQ-qPgPKlxQQYUL6qS743oXFzo5KceCp-8zs81602hhC5nnDiei7_vT0h-W24Fj</recordid><startdate>20010115</startdate><enddate>20010115</enddate><creator>Sebastiani, Silvia</creator><creator>Allavena, Paola</creator><creator>Albanesi, Cristina</creator><creator>Nasorri, Francesca</creator><creator>Bianchi, Giancarlo</creator><creator>Traidl, Claudia</creator><creator>Sozzani, Silvano</creator><creator>Girolomoni, Giampiero</creator><creator>Cavani, Andrea</creator><general>Am Assoc Immnol</general><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>7X8</scope></search><sort><creationdate>20010115</creationdate><title>Chemokine Receptor Expression and Function in CD4+ T Lymphocytes with Regulatory Activity</title><author>Sebastiani, Silvia ; Allavena, Paola ; Albanesi, Cristina ; Nasorri, Francesca ; Bianchi, Giancarlo ; Traidl, Claudia ; Sozzani, Silvano ; Girolomoni, Giampiero ; Cavani, Andrea</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c374t-866cb1bf4caf1d0764ddabc1ca252bc30101f94855226449aaa2d0398f04d2443</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>CD4-Positive T-Lymphocytes - immunology</topic><topic>CD4-Positive T-Lymphocytes - metabolism</topic><topic>Cell Line</topic><topic>Chemokine CCL1</topic><topic>Chemokines, CC - biosynthesis</topic><topic>Chemokines, CC - genetics</topic><topic>Chemokines, CC - metabolism</topic><topic>Chemotaxis, Leukocyte - immunology</topic><topic>Clone Cells</topic><topic>Cytokines - biosynthesis</topic><topic>Cytokines - genetics</topic><topic>Dermatitis, Allergic Contact - immunology</topic><topic>Epitopes, T-Lymphocyte - immunology</topic><topic>Humans</topic><topic>Interleukin-10 - biosynthesis</topic><topic>Interleukin-10 - genetics</topic><topic>Interphase - genetics</topic><topic>Interphase - immunology</topic><topic>Lymphocyte Activation - genetics</topic><topic>Nickel - immunology</topic><topic>Receptors, CCR8</topic><topic>Receptors, Chemokine - biosynthesis</topic><topic>Receptors, Chemokine - genetics</topic><topic>Receptors, Chemokine - physiology</topic><topic>RNA, Messenger - analysis</topic><topic>RNA, Messenger - biosynthesis</topic><topic>Signal Transduction - immunology</topic><topic>T-Lymphocyte Subsets - immunology</topic><topic>T-Lymphocyte Subsets - metabolism</topic><topic>Th1 Cells - immunology</topic><topic>Th1 Cells - metabolism</topic><topic>Th2 Cells - immunology</topic><topic>Th2 Cells - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sebastiani, Silvia</creatorcontrib><creatorcontrib>Allavena, Paola</creatorcontrib><creatorcontrib>Albanesi, Cristina</creatorcontrib><creatorcontrib>Nasorri, Francesca</creatorcontrib><creatorcontrib>Bianchi, Giancarlo</creatorcontrib><creatorcontrib>Traidl, Claudia</creatorcontrib><creatorcontrib>Sozzani, Silvano</creatorcontrib><creatorcontrib>Girolomoni, Giampiero</creatorcontrib><creatorcontrib>Cavani, Andrea</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of immunology (1950)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sebastiani, Silvia</au><au>Allavena, Paola</au><au>Albanesi, Cristina</au><au>Nasorri, Francesca</au><au>Bianchi, Giancarlo</au><au>Traidl, Claudia</au><au>Sozzani, Silvano</au><au>Girolomoni, Giampiero</au><au>Cavani, Andrea</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Chemokine Receptor Expression and Function in CD4+ T Lymphocytes with Regulatory Activity</atitle><jtitle>The Journal of immunology (1950)</jtitle><addtitle>J Immunol</addtitle><date>2001-01-15</date><risdate>2001</risdate><volume>166</volume><issue>2</issue><spage>996</spage><epage>1002</epage><pages>996-1002</pages><issn>0022-1767</issn><eissn>1550-6606</eissn><abstract>We have investigated the chemokine receptor expression and migratory behavior of a new subset of nickel-specific skin-homing regulatory CD4(+) T cells (Th(IL-10)) releasing high levels of IL-10, low IFN-gamma, and undetectable IL-4. These cells inhibit in a IL-10-dependent manner the capacity of dendritic cells to activate nickel-specific Tc1 and Th1 lymphocytes. RNase protection assay and FACS analysis revealed the expression of a vast repertoire of chemokine receptors on resting Th(IL-10), including the Th1-associated CXCR3 and CCR5, and the Th2-associated CCR3, CCR4, and CCR8, the latter at higher levels compared with Th2 cells. The most active chemokines for resting Th(IL-10), in terms of calcium mobilization and in vitro migration, were in order of potency: CCL2 (monocyte chemoattractant protein-1, CCR2 ligand), CCL4 (macrophage-inflammatory protein-1beta, CCR5 ligand), CCL3 (macrophage-inflammatory protein-1alpha, CCR1/5 ligand), CCL17 (thymus and activation-regulated chemokine, CCR4 ligand), CCL1 (I-309, CCR8 ligand), CXCL12 (stromal-derived factor-1, CXCR4), and CCL11 (eotaxin, CCR3 ligand). Consistent with receptor expression down-regulation, activated Th(IL-10) exhibited a reduced or absent response to most chemokines, but retained a significant migratory capacity to I-309, monocyte chemoattractant protein-1, and thymus and activation-regulated chemokine. I-309, which was ineffective on Th1 lymphocytes, attracted more efficiently Th(IL-10) than Th2 cells. I-309 and CCR8 mRNAs were not detected in unaffected skin and were up-regulated at the skin site of nickel-allergic reaction, with an earlier expression kinetics compared with IL-10 and IL-4. Results indicate that skin-homing regulatory Th(IL-10) lymphocytes coexpress functional Th1- and Th2-associated chemokine receptors, and that CCR8/I-309-driven recruitment of both resting and activated Th(IL-10) cells may be critically involved in the regulation of Th1-mediated skin allergic disorders.</abstract><cop>United States</cop><pub>Am Assoc Immnol</pub><pmid>11145678</pmid><doi>10.4049/jimmunol.166.2.996</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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subjects | CD4-Positive T-Lymphocytes - immunology CD4-Positive T-Lymphocytes - metabolism Cell Line Chemokine CCL1 Chemokines, CC - biosynthesis Chemokines, CC - genetics Chemokines, CC - metabolism Chemotaxis, Leukocyte - immunology Clone Cells Cytokines - biosynthesis Cytokines - genetics Dermatitis, Allergic Contact - immunology Epitopes, T-Lymphocyte - immunology Humans Interleukin-10 - biosynthesis Interleukin-10 - genetics Interphase - genetics Interphase - immunology Lymphocyte Activation - genetics Nickel - immunology Receptors, CCR8 Receptors, Chemokine - biosynthesis Receptors, Chemokine - genetics Receptors, Chemokine - physiology RNA, Messenger - analysis RNA, Messenger - biosynthesis Signal Transduction - immunology T-Lymphocyte Subsets - immunology T-Lymphocyte Subsets - metabolism Th1 Cells - immunology Th1 Cells - metabolism Th2 Cells - immunology Th2 Cells - metabolism |
title | Chemokine Receptor Expression and Function in CD4+ T Lymphocytes with Regulatory Activity |
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