T cell activation inhibitors reduce CD8+ T cell and pro-inflammatory macrophage accumulation in adipose tissue of obese mice
Adipose tissue inflammation and specifically, pro-inflammatory macrophages are believed to contribute to insulin resistance (IR) in obesity in humans and animal models. Recent studies have invoked T cells in the recruitment of pro-inflammatory macrophages and the development of IR. To test the role...
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| creator | Montes, Vince N Turner, Michael S Subramanian, Savitha Ding, Yilei Hayden-Ledbetter, Martha Slater, Sonya Goodspeed, Leela Wang, Shari Omer, Mohamed Den Hartigh, Laura J Averill, Michelle M O'Brien, Kevin D Ledbetter, Jeffrey Chait, Alan |
| description | Adipose tissue inflammation and specifically, pro-inflammatory macrophages are believed to contribute to insulin resistance (IR) in obesity in humans and animal models. Recent studies have invoked T cells in the recruitment of pro-inflammatory macrophages and the development of IR. To test the role of the T cell response in adipose tissue of mice fed an obesogenic diet, we used two agents (CTLA-4 Ig and anti-CD40L antibody) that block co-stimulation, which is essential for full T cell activation. C57BL/6 mice were fed an obesogenic diet for 16 weeks, and concomitantly either treated with CTLA-4 Ig, anti-CD40L antibody or an IgG control (300 µg/week). The treatments altered the immune cell composition of adipose tissue in obese mice. Treated mice demonstrated a marked reduction in pro-inflammatory adipose tissue macrophages and activated CD8+ T cells. Mice treated with anti-CD40L exhibited reduced weight gain, which was accompanied by a trend toward improved IR. CTLA-4 Ig treatment, however, was not associated with improved IR. These data suggest that the presence of pro-inflammatory T cells and macrophages can be altered with co-stimulatory inhibitors, but may not be a significant contributor to the whole body IR phenotype. |
| doi_str_mv | 10.1371/journal.pone.0067709 |
| format | Article |
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Recent studies have invoked T cells in the recruitment of pro-inflammatory macrophages and the development of IR. To test the role of the T cell response in adipose tissue of mice fed an obesogenic diet, we used two agents (CTLA-4 Ig and anti-CD40L antibody) that block co-stimulation, which is essential for full T cell activation. C57BL/6 mice were fed an obesogenic diet for 16 weeks, and concomitantly either treated with CTLA-4 Ig, anti-CD40L antibody or an IgG control (300 µg/week). The treatments altered the immune cell composition of adipose tissue in obese mice. Treated mice demonstrated a marked reduction in pro-inflammatory adipose tissue macrophages and activated CD8+ T cells. Mice treated with anti-CD40L exhibited reduced weight gain, which was accompanied by a trend toward improved IR. CTLA-4 Ig treatment, however, was not associated with improved IR. These data suggest that the presence of pro-inflammatory T cells and macrophages can be altered with co-stimulatory inhibitors, but may not be a significant contributor to the whole body IR phenotype.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0067709</identifier><identifier>PMID: 23844072</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adipose tissue ; Adipose Tissue - drug effects ; Adipose Tissue - immunology ; Adipose Tissue - pathology ; Analysis ; Animal models ; Animal tissues ; Animals ; Bioaccumulation ; Biology ; Body fat ; Body weight gain ; CD40 Ligand - antagonists & inhibitors ; CD40 Ligand - immunology ; CD40L protein ; CD8 antigen ; CD8-Positive T-Lymphocytes - drug effects ; CD8-Positive T-Lymphocytes - immunology ; CD8-Positive T-Lymphocytes - pathology ; Cell activation ; CTLA-4 Antigen - antagonists & inhibitors ; CTLA-4 Antigen - immunology ; CTLA-4 protein ; Diet, High-Fat ; Genetic aspects ; Immunoglobulin G ; Immunoglobulins - administration & dosage ; Immunomodulation ; Inflammation ; Inflammation - immunology ; Inflammation - pathology ; Inhibitors ; Insulin ; Insulin resistance ; Insulin Resistance - immunology ; Lymphocyte Activation - drug effects ; Lymphocytes ; Lymphocytes T ; Macrophages ; Macrophages - drug effects ; Macrophages - immunology ; Macrophages - pathology ; Male ; Medicine ; Mice ; Mice, Inbred C57BL ; Mice, Obese ; Nutrition ; Obesity ; Obesity - immunology ; Obesity - pathology ; Recruitment ; Rodents ; T cell receptors ; T cells ; Weight Gain - drug effects ; Weight Gain - immunology ; Weight reduction</subject><ispartof>PloS one, 2013-07, Vol.8 (7), p.e67709-e67709</ispartof><rights>COPYRIGHT 2013 Public Library of Science</rights><rights>2013 Montes et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2013 Montes et al 2013 Montes et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-5ca1d314423e7881621a1b7c0c7d92629cbb4b1ba3d21e19369341582a99ad943</citedby><cites>FETCH-LOGICAL-c692t-5ca1d314423e7881621a1b7c0c7d92629cbb4b1ba3d21e19369341582a99ad943</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3699637/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3699637/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79343,79344</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23844072$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Cignarella, Andrea</contributor><creatorcontrib>Montes, Vince N</creatorcontrib><creatorcontrib>Turner, Michael S</creatorcontrib><creatorcontrib>Subramanian, Savitha</creatorcontrib><creatorcontrib>Ding, Yilei</creatorcontrib><creatorcontrib>Hayden-Ledbetter, Martha</creatorcontrib><creatorcontrib>Slater, Sonya</creatorcontrib><creatorcontrib>Goodspeed, Leela</creatorcontrib><creatorcontrib>Wang, Shari</creatorcontrib><creatorcontrib>Omer, Mohamed</creatorcontrib><creatorcontrib>Den Hartigh, Laura J</creatorcontrib><creatorcontrib>Averill, Michelle M</creatorcontrib><creatorcontrib>O'Brien, Kevin D</creatorcontrib><creatorcontrib>Ledbetter, Jeffrey</creatorcontrib><creatorcontrib>Chait, Alan</creatorcontrib><title>T cell activation inhibitors reduce CD8+ T cell and pro-inflammatory macrophage accumulation in adipose tissue of obese mice</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Adipose tissue inflammation and specifically, pro-inflammatory macrophages are believed to contribute to insulin resistance (IR) in obesity in humans and animal models. Recent studies have invoked T cells in the recruitment of pro-inflammatory macrophages and the development of IR. To test the role of the T cell response in adipose tissue of mice fed an obesogenic diet, we used two agents (CTLA-4 Ig and anti-CD40L antibody) that block co-stimulation, which is essential for full T cell activation. C57BL/6 mice were fed an obesogenic diet for 16 weeks, and concomitantly either treated with CTLA-4 Ig, anti-CD40L antibody or an IgG control (300 µg/week). The treatments altered the immune cell composition of adipose tissue in obese mice. Treated mice demonstrated a marked reduction in pro-inflammatory adipose tissue macrophages and activated CD8+ T cells. Mice treated with anti-CD40L exhibited reduced weight gain, which was accompanied by a trend toward improved IR. CTLA-4 Ig treatment, however, was not associated with improved IR. 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antagonists & inhibitors</subject><subject>CTLA-4 Antigen - immunology</subject><subject>CTLA-4 protein</subject><subject>Diet, High-Fat</subject><subject>Genetic aspects</subject><subject>Immunoglobulin G</subject><subject>Immunoglobulins - administration & dosage</subject><subject>Immunomodulation</subject><subject>Inflammation</subject><subject>Inflammation - immunology</subject><subject>Inflammation - pathology</subject><subject>Inhibitors</subject><subject>Insulin</subject><subject>Insulin resistance</subject><subject>Insulin Resistance - immunology</subject><subject>Lymphocyte Activation - drug effects</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Macrophages</subject><subject>Macrophages - drug effects</subject><subject>Macrophages - immunology</subject><subject>Macrophages - pathology</subject><subject>Male</subject><subject>Medicine</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Obese</subject><subject>Nutrition</subject><subject>Obesity</subject><subject>Obesity - immunology</subject><subject>Obesity - pathology</subject><subject>Recruitment</subject><subject>Rodents</subject><subject>T cell receptors</subject><subject>T cells</subject><subject>Weight Gain - drug effects</subject><subject>Weight Gain - immunology</subject><subject>Weight reduction</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk12L1DAUhoso7rr6D0QDgigyY76maW6EZfwaWFjQ1dtwkqYzGdqmm7SLC_54M05nmcpeSC_apM95c86bc7LsOcFzwgR5v_VDaKGed761c4xzIbB8kJ0Syegsp5g9PPo-yZ7EuMV4wYo8f5ydUFZwjgU9zX5fIWPrGoHp3Q30zrfItRunXe9DRMGWg7Fo-bF4hw5gW6Iu-JlrqxqaBhJ3ixowwXcbWNskZIZmqA9SCErX-WhR72IcLPIV8tqmdeOMfZo9qqCO9tn4Pst-fP50tfw6u7j8slqeX8xMLmk_WxggJSOcU2ZFUZCcEiBaGGxEKWlOpdGaa6KBlZTYVHQuGSeLgoKUUErOzrKXe92u9lGNxkVFOM2lwLyQiVjtidLDVnXBNRBulQen_m74sFYQemdqq5L3BNsSa0s0l8C1LoWgTNtikRte0aT1YTxt0I0tjW37APVEdPqndRu19jcq5S1zJpLAm1Eg-OvBxl41Lu7Mh9b6IeXNpEx1JysS-uof9P7qRmoNqYB0cz6da3ai6pyL1AqcFru85_dQ6SltuqzUZZVL-5OAt5OAxPT2V7-GIUa1-v7t_9nLn1P29RG7sVD3m-jrYddScQryPZi6L8ZgqzuTCVa7ITm4oXZDosYhSWEvji_oLugwFewPKxIMVA</recordid><startdate>20130702</startdate><enddate>20130702</enddate><creator>Montes, Vince N</creator><creator>Turner, Michael S</creator><creator>Subramanian, Savitha</creator><creator>Ding, Yilei</creator><creator>Hayden-Ledbetter, Martha</creator><creator>Slater, Sonya</creator><creator>Goodspeed, Leela</creator><creator>Wang, Shari</creator><creator>Omer, Mohamed</creator><creator>Den Hartigh, Laura J</creator><creator>Averill, Michelle M</creator><creator>O'Brien, Kevin D</creator><creator>Ledbetter, Jeffrey</creator><creator>Chait, Alan</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20130702</creationdate><title>T cell activation inhibitors reduce CD8+ T cell and pro-inflammatory macrophage accumulation in adipose tissue of obese mice</title><author>Montes, Vince N ; Turner, Michael S ; Subramanian, Savitha ; Ding, Yilei ; Hayden-Ledbetter, Martha ; Slater, Sonya ; Goodspeed, Leela ; Wang, Shari ; Omer, Mohamed ; Den Hartigh, Laura J ; Averill, Michelle M ; O'Brien, Kevin D ; Ledbetter, Jeffrey ; Chait, Alan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-5ca1d314423e7881621a1b7c0c7d92629cbb4b1ba3d21e19369341582a99ad943</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Adipose tissue</topic><topic>Adipose Tissue - 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Recent studies have invoked T cells in the recruitment of pro-inflammatory macrophages and the development of IR. To test the role of the T cell response in adipose tissue of mice fed an obesogenic diet, we used two agents (CTLA-4 Ig and anti-CD40L antibody) that block co-stimulation, which is essential for full T cell activation. C57BL/6 mice were fed an obesogenic diet for 16 weeks, and concomitantly either treated with CTLA-4 Ig, anti-CD40L antibody or an IgG control (300 µg/week). The treatments altered the immune cell composition of adipose tissue in obese mice. Treated mice demonstrated a marked reduction in pro-inflammatory adipose tissue macrophages and activated CD8+ T cells. Mice treated with anti-CD40L exhibited reduced weight gain, which was accompanied by a trend toward improved IR. CTLA-4 Ig treatment, however, was not associated with improved IR. These data suggest that the presence of pro-inflammatory T cells and macrophages can be altered with co-stimulatory inhibitors, but may not be a significant contributor to the whole body IR phenotype.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23844072</pmid><doi>10.1371/journal.pone.0067709</doi><tpages>e67709</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2013-07, Vol.8 (7), p.e67709-e67709 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1426970489 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Adipose tissue Adipose Tissue - drug effects Adipose Tissue - immunology Adipose Tissue - pathology Analysis Animal models Animal tissues Animals Bioaccumulation Biology Body fat Body weight gain CD40 Ligand - antagonists & inhibitors CD40 Ligand - immunology CD40L protein CD8 antigen CD8-Positive T-Lymphocytes - drug effects CD8-Positive T-Lymphocytes - immunology CD8-Positive T-Lymphocytes - pathology Cell activation CTLA-4 Antigen - antagonists & inhibitors CTLA-4 Antigen - immunology CTLA-4 protein Diet, High-Fat Genetic aspects Immunoglobulin G Immunoglobulins - administration & dosage Immunomodulation Inflammation Inflammation - immunology Inflammation - pathology Inhibitors Insulin Insulin resistance Insulin Resistance - immunology Lymphocyte Activation - drug effects Lymphocytes Lymphocytes T Macrophages Macrophages - drug effects Macrophages - immunology Macrophages - pathology Male Medicine Mice Mice, Inbred C57BL Mice, Obese Nutrition Obesity Obesity - immunology Obesity - pathology Recruitment Rodents T cell receptors T cells Weight Gain - drug effects Weight Gain - immunology Weight reduction |
| title | T cell activation inhibitors reduce CD8+ T cell and pro-inflammatory macrophage accumulation in adipose tissue of obese mice |
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