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Clonal Th2 cells associated with chronic hypereosinophilia: TARC‐induced CCR4 down‐regulation in vivo
We analyzed the expression of chemokine receptors on clonal Th2‐type CD4+CD3– lymphocytes isolated from blood of two patients with chronic hypereosinophilia. First, we observed that these Th2 cells express membrane CCR5 and CXCR4 but neither CCR3 nor CCR4 when analyzed immediately after purification...
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| Published in: | European journal of immunology 2001-04, Vol.31 (4), p.1037-1046 |
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| container_end_page | 1046 |
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| container_title | European journal of immunology |
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| creator | de Lavareille, Aurore Roufosse, Florence Schandené, Liliane Stordeur, Patrick Cogan, Elie Goldman, Michel |
| description | We analyzed the expression of chemokine receptors on clonal Th2‐type CD4+CD3– lymphocytes isolated from blood of two patients with chronic hypereosinophilia. First, we observed that these Th2 cells express membrane CCR5 and CXCR4 but neither CCR3 nor CCR4 when analyzed immediately after purification. However, CCR4 appeared following culture in human serum‐free medium, suggesting that it was down‐regulated in vivo. Indeed, patient's serum, but not control human serum, strongly down‐regulated CCR4 expression on cultured Th2 cells. As high levels of TARC, a CCR4 ligand, were detected in the serum of four hypereosinophilic patients with CD3‐CD4+ clonal Th2 cells, we evaluated the effect of TARC neutralization in this system. Addition of a neutralizing anti‐TARC mAb inhibited CCR4 down‐regulation by patient's serum, indicating that circulating TARC contributed to CCR4 down‐regulation on Th2 cells in vivo. Clonal Th2 cells did not secrete high levels of TARC themselves but induced a sustained production of TARC by monocyte‐derived dendritic cells, a phenomenon that was inhibited by addition of blocking mAb against IL‐4 receptor. We conclude that high circulating levels of TARC in serum of patients with chronic hypereosinophilia, most likely derived from antigen‐presenting cells stimulated by Th2‐type cytokines, induce down‐regulation of CCR4 on Th2 cells in vivo. |
| doi_str_mv | 10.1002/1521-4141(200104)31:4<1037::AID-IMMU1037>3.0.CO;2-# |
| format | article |
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First, we observed that these Th2 cells express membrane CCR5 and CXCR4 but neither CCR3 nor CCR4 when analyzed immediately after purification. However, CCR4 appeared following culture in human serum‐free medium, suggesting that it was down‐regulated in vivo. Indeed, patient's serum, but not control human serum, strongly down‐regulated CCR4 expression on cultured Th2 cells. As high levels of TARC, a CCR4 ligand, were detected in the serum of four hypereosinophilic patients with CD3‐CD4+ clonal Th2 cells, we evaluated the effect of TARC neutralization in this system. Addition of a neutralizing anti‐TARC mAb inhibited CCR4 down‐regulation by patient's serum, indicating that circulating TARC contributed to CCR4 down‐regulation on Th2 cells in vivo. Clonal Th2 cells did not secrete high levels of TARC themselves but induced a sustained production of TARC by monocyte‐derived dendritic cells, a phenomenon that was inhibited by addition of blocking mAb against IL‐4 receptor. We conclude that high circulating levels of TARC in serum of patients with chronic hypereosinophilia, most likely derived from antigen‐presenting cells stimulated by Th2‐type cytokines, induce down‐regulation of CCR4 on Th2 cells in vivo.</description><identifier>ISSN: 0014-2980</identifier><identifier>EISSN: 1521-4141</identifier><identifier>DOI: 10.1002/1521-4141(200104)31:4<1037::AID-IMMU1037>3.0.CO;2-#</identifier><identifier>PMID: 11298328</identifier><language>eng</language><publisher>Weinheim: WILEY‐VCH Verlag GmbH</publisher><subject>Adult ; Calcium - metabolism ; Calcium Signaling - drug effects ; CCR4 ; CCR4 protein ; Cells, Cultured ; Chemokine CCL11 ; Chemokine CCL17 ; Chemokine CCL22 ; Chemokine CCL5 - pharmacology ; Chemokine CXCL12 ; Chemokines, CC - biosynthesis ; Chemokines, CC - blood ; Chemokines, CC - metabolism ; Chemokines, CC - pharmacology ; Chemotaxis, Leukocyte - drug effects ; Chronic Disease ; Clone Cells - drug effects ; Clone Cells - metabolism ; Clone Cells - pathology ; Coculture Techniques ; Cytokines - pharmacology ; Dendritic cell ; Dendritic Cells - cytology ; Dendritic Cells - drug effects ; Dendritic Cells - metabolism ; Down-Regulation - drug effects ; Female ; Flow Cytometry ; Humans ; hypereosinophilia ; Hypereosinophilic syndrome ; Hypereosinophilic Syndrome - metabolism ; Hypereosinophilic Syndrome - pathology ; Interleukin-13 - pharmacology ; Interleukin-4 - pharmacology ; Middle Aged ; Receptors, CCR4 ; Receptors, Chemokine - metabolism ; TARC ; TARC protein ; Th2 Cells - drug effects ; Th2 Cells - metabolism ; Th2 Cells - pathology ; Th2 clone</subject><ispartof>European journal of immunology, 2001-04, Vol.31 (4), p.1037-1046</ispartof><rights>WILEY‐VCH Verlag GmbH, Weinheim, Fed. 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First, we observed that these Th2 cells express membrane CCR5 and CXCR4 but neither CCR3 nor CCR4 when analyzed immediately after purification. However, CCR4 appeared following culture in human serum‐free medium, suggesting that it was down‐regulated in vivo. Indeed, patient's serum, but not control human serum, strongly down‐regulated CCR4 expression on cultured Th2 cells. As high levels of TARC, a CCR4 ligand, were detected in the serum of four hypereosinophilic patients with CD3‐CD4+ clonal Th2 cells, we evaluated the effect of TARC neutralization in this system. Addition of a neutralizing anti‐TARC mAb inhibited CCR4 down‐regulation by patient's serum, indicating that circulating TARC contributed to CCR4 down‐regulation on Th2 cells in vivo. Clonal Th2 cells did not secrete high levels of TARC themselves but induced a sustained production of TARC by monocyte‐derived dendritic cells, a phenomenon that was inhibited by addition of blocking mAb against IL‐4 receptor. We conclude that high circulating levels of TARC in serum of patients with chronic hypereosinophilia, most likely derived from antigen‐presenting cells stimulated by Th2‐type cytokines, induce down‐regulation of CCR4 on Th2 cells in vivo.</description><subject>Adult</subject><subject>Calcium - metabolism</subject><subject>Calcium Signaling - drug effects</subject><subject>CCR4</subject><subject>CCR4 protein</subject><subject>Cells, Cultured</subject><subject>Chemokine CCL11</subject><subject>Chemokine CCL17</subject><subject>Chemokine CCL22</subject><subject>Chemokine CCL5 - pharmacology</subject><subject>Chemokine CXCL12</subject><subject>Chemokines, CC - biosynthesis</subject><subject>Chemokines, CC - blood</subject><subject>Chemokines, CC - metabolism</subject><subject>Chemokines, CC - pharmacology</subject><subject>Chemotaxis, Leukocyte - drug effects</subject><subject>Chronic Disease</subject><subject>Clone Cells - drug effects</subject><subject>Clone Cells - metabolism</subject><subject>Clone Cells - pathology</subject><subject>Coculture Techniques</subject><subject>Cytokines - pharmacology</subject><subject>Dendritic cell</subject><subject>Dendritic Cells - cytology</subject><subject>Dendritic Cells - drug effects</subject><subject>Dendritic Cells - metabolism</subject><subject>Down-Regulation - drug effects</subject><subject>Female</subject><subject>Flow Cytometry</subject><subject>Humans</subject><subject>hypereosinophilia</subject><subject>Hypereosinophilic syndrome</subject><subject>Hypereosinophilic Syndrome - metabolism</subject><subject>Hypereosinophilic Syndrome - pathology</subject><subject>Interleukin-13 - pharmacology</subject><subject>Interleukin-4 - pharmacology</subject><subject>Middle Aged</subject><subject>Receptors, CCR4</subject><subject>Receptors, Chemokine - metabolism</subject><subject>TARC</subject><subject>TARC protein</subject><subject>Th2 Cells - drug effects</subject><subject>Th2 Cells - metabolism</subject><subject>Th2 Cells - pathology</subject><subject>Th2 clone</subject><issn>0014-2980</issn><issn>1521-4141</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><recordid>eNqVkd-K1DAUxoMo7rj6ChIQZL3oePKnSTMrC0PV3YFdBpdZb0OapjbSacZmusPc-Qg-o09iy4zrjSBehfPxO99HzofQOYEpAaBvSUpJwgknZxSAAH_DyIy_I8DkbDZfvE8WNzd343TBpjDNl-c0efUITR62HqPJsMYTqjI4Qc9i_AoASqTqKTohZFAZzSbI501oTYNXNcXWNU3EJsZgvdm6Eu_8tsa27kLrLa73G9e5EH0bNrVvvJnh1fw2__n9h2_L3g54nt9yXIZdO2id-9I3ZutDi32L7_19eI6eVKaJ7sXxPUV3Hz-s8qvkenm5yOfXiWWUyaRUYGWaVqwQsiCQVSLLgJWuYgCWCgnSKSUqnvG0EGnh0lIIqxwvhOHKOMtO0euD76YL33oXt3rt4_g107rQRy0lcEUY-SdIMpCSAB3ATwfQdiHGzlV60_m16faagB6r0uPR9Xh0fahKs2HUYzlaD1Xp31VppkHnSz16vjyG98XalX8cj80MwOcDsPON2_9P4l8DHxT2C6V6rYo</recordid><startdate>200104</startdate><enddate>200104</enddate><creator>de Lavareille, Aurore</creator><creator>Roufosse, Florence</creator><creator>Schandené, Liliane</creator><creator>Stordeur, Patrick</creator><creator>Cogan, Elie</creator><creator>Goldman, Michel</creator><general>WILEY‐VCH Verlag GmbH</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>7T5</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>200104</creationdate><title>Clonal Th2 cells associated with chronic hypereosinophilia: TARC‐induced CCR4 down‐regulation in vivo</title><author>de Lavareille, Aurore ; Roufosse, Florence ; Schandené, Liliane ; Stordeur, Patrick ; Cogan, Elie ; Goldman, Michel</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3237-d90c755f3b67b108f68803def300c26707e996f4845b65be5d66c9e4b6a49aec3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Adult</topic><topic>Calcium - metabolism</topic><topic>Calcium Signaling - drug effects</topic><topic>CCR4</topic><topic>CCR4 protein</topic><topic>Cells, Cultured</topic><topic>Chemokine CCL11</topic><topic>Chemokine CCL17</topic><topic>Chemokine CCL22</topic><topic>Chemokine CCL5 - pharmacology</topic><topic>Chemokine CXCL12</topic><topic>Chemokines, CC - biosynthesis</topic><topic>Chemokines, CC - blood</topic><topic>Chemokines, CC - metabolism</topic><topic>Chemokines, CC - pharmacology</topic><topic>Chemotaxis, Leukocyte - drug effects</topic><topic>Chronic Disease</topic><topic>Clone Cells - drug effects</topic><topic>Clone Cells - metabolism</topic><topic>Clone Cells - pathology</topic><topic>Coculture Techniques</topic><topic>Cytokines - pharmacology</topic><topic>Dendritic cell</topic><topic>Dendritic Cells - cytology</topic><topic>Dendritic Cells - drug effects</topic><topic>Dendritic Cells - metabolism</topic><topic>Down-Regulation - drug effects</topic><topic>Female</topic><topic>Flow Cytometry</topic><topic>Humans</topic><topic>hypereosinophilia</topic><topic>Hypereosinophilic syndrome</topic><topic>Hypereosinophilic Syndrome - metabolism</topic><topic>Hypereosinophilic Syndrome - pathology</topic><topic>Interleukin-13 - pharmacology</topic><topic>Interleukin-4 - pharmacology</topic><topic>Middle Aged</topic><topic>Receptors, CCR4</topic><topic>Receptors, Chemokine - metabolism</topic><topic>TARC</topic><topic>TARC protein</topic><topic>Th2 Cells - drug effects</topic><topic>Th2 Cells - metabolism</topic><topic>Th2 Cells - pathology</topic><topic>Th2 clone</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>de Lavareille, Aurore</creatorcontrib><creatorcontrib>Roufosse, Florence</creatorcontrib><creatorcontrib>Schandené, Liliane</creatorcontrib><creatorcontrib>Stordeur, Patrick</creatorcontrib><creatorcontrib>Cogan, Elie</creatorcontrib><creatorcontrib>Goldman, Michel</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><jtitle>European journal of immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>de Lavareille, Aurore</au><au>Roufosse, Florence</au><au>Schandené, Liliane</au><au>Stordeur, Patrick</au><au>Cogan, Elie</au><au>Goldman, Michel</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Clonal Th2 cells associated with chronic hypereosinophilia: TARC‐induced CCR4 down‐regulation in vivo</atitle><jtitle>European journal of immunology</jtitle><addtitle>Eur J Immunol</addtitle><date>2001-04</date><risdate>2001</risdate><volume>31</volume><issue>4</issue><spage>1037</spage><epage>1046</epage><pages>1037-1046</pages><issn>0014-2980</issn><eissn>1521-4141</eissn><notes>ObjectType-Article-2</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-1</notes><notes>content type line 23</notes><notes>ObjectType-Article-1</notes><notes>ObjectType-Feature-2</notes><abstract>We analyzed the expression of chemokine receptors on clonal Th2‐type CD4+CD3– lymphocytes isolated from blood of two patients with chronic hypereosinophilia. First, we observed that these Th2 cells express membrane CCR5 and CXCR4 but neither CCR3 nor CCR4 when analyzed immediately after purification. However, CCR4 appeared following culture in human serum‐free medium, suggesting that it was down‐regulated in vivo. Indeed, patient's serum, but not control human serum, strongly down‐regulated CCR4 expression on cultured Th2 cells. As high levels of TARC, a CCR4 ligand, were detected in the serum of four hypereosinophilic patients with CD3‐CD4+ clonal Th2 cells, we evaluated the effect of TARC neutralization in this system. Addition of a neutralizing anti‐TARC mAb inhibited CCR4 down‐regulation by patient's serum, indicating that circulating TARC contributed to CCR4 down‐regulation on Th2 cells in vivo. Clonal Th2 cells did not secrete high levels of TARC themselves but induced a sustained production of TARC by monocyte‐derived dendritic cells, a phenomenon that was inhibited by addition of blocking mAb against IL‐4 receptor. We conclude that high circulating levels of TARC in serum of patients with chronic hypereosinophilia, most likely derived from antigen‐presenting cells stimulated by Th2‐type cytokines, induce down‐regulation of CCR4 on Th2 cells in vivo.</abstract><cop>Weinheim</cop><pub>WILEY‐VCH Verlag GmbH</pub><pmid>11298328</pmid><doi>10.1002/1521-4141(200104)31:4<1037::AID-IMMU1037>3.0.CO;2-#</doi><tpages>10</tpages></addata></record> |
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| ispartof | European journal of immunology, 2001-04, Vol.31 (4), p.1037-1046 |
| issn | 0014-2980 1521-4141 |
| language | eng |
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| source | Wiley-Blackwell Journals |
| subjects | Adult Calcium - metabolism Calcium Signaling - drug effects CCR4 CCR4 protein Cells, Cultured Chemokine CCL11 Chemokine CCL17 Chemokine CCL22 Chemokine CCL5 - pharmacology Chemokine CXCL12 Chemokines, CC - biosynthesis Chemokines, CC - blood Chemokines, CC - metabolism Chemokines, CC - pharmacology Chemotaxis, Leukocyte - drug effects Chronic Disease Clone Cells - drug effects Clone Cells - metabolism Clone Cells - pathology Coculture Techniques Cytokines - pharmacology Dendritic cell Dendritic Cells - cytology Dendritic Cells - drug effects Dendritic Cells - metabolism Down-Regulation - drug effects Female Flow Cytometry Humans hypereosinophilia Hypereosinophilic syndrome Hypereosinophilic Syndrome - metabolism Hypereosinophilic Syndrome - pathology Interleukin-13 - pharmacology Interleukin-4 - pharmacology Middle Aged Receptors, CCR4 Receptors, Chemokine - metabolism TARC TARC protein Th2 Cells - drug effects Th2 Cells - metabolism Th2 Cells - pathology Th2 clone |
| title | Clonal Th2 cells associated with chronic hypereosinophilia: TARC‐induced CCR4 down‐regulation in vivo |
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