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
Hauptverfasser: Sebastiani, Silvia, Allavena, Paola, Albanesi, Cristina, Nasorri, Francesca, Bianchi, Giancarlo, Traidl, Claudia, Sozzani, Silvano, Girolomoni, Giampiero, Cavani, Andrea
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container_title The Journal of immunology (1950)
container_volume 166
creator Sebastiani, Silvia
Allavena, Paola
Albanesi, Cristina
Nasorri, Francesca
Bianchi, Giancarlo
Traidl, Claudia
Sozzani, Silvano
Girolomoni, Giampiero
Cavani, Andrea
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.
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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 ; 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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.</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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