Functional Modulation of Regulatory T Cells by IL-2
The suppressive function of regulatory T cells (Tregs) is critical to the maintenance of immune homeostasis in vivo and yet, the specific identification of Tregs by phenotypic markers is not perfect. Tregs were originally identified in the CD4+CD25+ fraction of T cells, but FoxP3 expression was late...
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| description | The suppressive function of regulatory T cells (Tregs) is critical to the maintenance of immune homeostasis in vivo and yet, the specific identification of Tregs by phenotypic markers is not perfect. Tregs were originally identified in the CD4+CD25+ fraction of T cells, but FoxP3 expression was later included as an additional marker of Tregs as FoxP3 expression was identified as being critical to the development and function of these cells. Intracellular expression of FoxP3 makes it difficult in using to isolate live and not permeabilized cells for functional assays. As such CD4+CD25+ fraction is still frequently used for functional assays of Tregs. Although, the CD4+CD25+ fraction substantially overlaps with the FoxP3+ fraction, the minor mismatch between CD4+CD25+ and FoxP3+ fractions may confound the functional characteristics of Tregs. In this study, we isolated CD4+FoxP3+ as well as CD4+CD25+ fractions from Foxp3 knock-in mice, and compared their proliferative and suppressive activity in the presence or absence of various concentrations of IL-2. Our results showed comparable patterns of proliferative and suppressive responses for both fractions, except that contrary to the CD4+CD25+ fraction the FoxP3+ fraction did not proliferate in an autocrine fashion even in response to a strong stimulation. In presence of exogenous IL-2, both CD4+CD25+ and CD4+FoxP3+ fractions were more sensitive than the CD4+CD25- responder cells in proliferative responsiveness. In addition, a low dose IL-2 enhanced whereas a high dose abrogated the suppressive activities of the CD4+CD25+ and CD4+FoxP3+ fractions. These results may provide an additional understanding of the characteristics of the various fractions of isolated Tregs based on phenotype and function and the role of varying levels of exogenous IL-2 on the suppressive activity of these cells. |
| doi_str_mv | 10.1371/journal.pone.0141864 |
| format | Article |
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Tregs were originally identified in the CD4+CD25+ fraction of T cells, but FoxP3 expression was later included as an additional marker of Tregs as FoxP3 expression was identified as being critical to the development and function of these cells. Intracellular expression of FoxP3 makes it difficult in using to isolate live and not permeabilized cells for functional assays. As such CD4+CD25+ fraction is still frequently used for functional assays of Tregs. Although, the CD4+CD25+ fraction substantially overlaps with the FoxP3+ fraction, the minor mismatch between CD4+CD25+ and FoxP3+ fractions may confound the functional characteristics of Tregs. In this study, we isolated CD4+FoxP3+ as well as CD4+CD25+ fractions from Foxp3 knock-in mice, and compared their proliferative and suppressive activity in the presence or absence of various concentrations of IL-2. Our results showed comparable patterns of proliferative and suppressive responses for both fractions, except that contrary to the CD4+CD25+ fraction the FoxP3+ fraction did not proliferate in an autocrine fashion even in response to a strong stimulation. In presence of exogenous IL-2, both CD4+CD25+ and CD4+FoxP3+ fractions were more sensitive than the CD4+CD25- responder cells in proliferative responsiveness. In addition, a low dose IL-2 enhanced whereas a high dose abrogated the suppressive activities of the CD4+CD25+ and CD4+FoxP3+ fractions. 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This is an open access article distributed under the terms of the Creative Commons Attribution License: http://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>2015 Moon et al 2015 Moon et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-363ab4f87edc3cb1db7aa5122b313a942d76bde3dfb58d7d37a3011585e264f3</citedby><cites>FETCH-LOGICAL-c692t-363ab4f87edc3cb1db7aa5122b313a942d76bde3dfb58d7d37a3011585e264f3</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/PMC4631326/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4631326/$$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/26529512$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Moon, Byung-In</creatorcontrib><creatorcontrib>Kim, Tae Hun</creatorcontrib><creatorcontrib>Seoh, Ju-Young</creatorcontrib><title>Functional Modulation of Regulatory T Cells by IL-2</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>The suppressive function of regulatory T cells (Tregs) is critical to the maintenance of immune homeostasis in vivo and yet, the specific identification of Tregs by phenotypic markers is not perfect. Tregs were originally identified in the CD4+CD25+ fraction of T cells, but FoxP3 expression was later included as an additional marker of Tregs as FoxP3 expression was identified as being critical to the development and function of these cells. Intracellular expression of FoxP3 makes it difficult in using to isolate live and not permeabilized cells for functional assays. As such CD4+CD25+ fraction is still frequently used for functional assays of Tregs. Although, the CD4+CD25+ fraction substantially overlaps with the FoxP3+ fraction, the minor mismatch between CD4+CD25+ and FoxP3+ fractions may confound the functional characteristics of Tregs. In this study, we isolated CD4+FoxP3+ as well as CD4+CD25+ fractions from Foxp3 knock-in mice, and compared their proliferative and suppressive activity in the presence or absence of various concentrations of IL-2. Our results showed comparable patterns of proliferative and suppressive responses for both fractions, except that contrary to the CD4+CD25+ fraction the FoxP3+ fraction did not proliferate in an autocrine fashion even in response to a strong stimulation. In presence of exogenous IL-2, both CD4+CD25+ and CD4+FoxP3+ fractions were more sensitive than the CD4+CD25- responder cells in proliferative responsiveness. In addition, a low dose IL-2 enhanced whereas a high dose abrogated the suppressive activities of the CD4+CD25+ and CD4+FoxP3+ fractions. These results may provide an additional understanding of the characteristics of the various fractions of isolated Tregs based on phenotype and function and the role of varying levels of exogenous IL-2 on the suppressive activity of these cells.</description><subject>Animals</subject><subject>Autocrine signalling</subject><subject>B cells</subject><subject>Biological markers</subject><subject>CD25 antigen</subject><subject>CD4 antigen</subject><subject>CD4 Antigens - genetics</subject><subject>CD4 Antigens - immunology</subject><subject>Cytokines</subject><subject>Diabetes</subject><subject>Drug dosages</subject><subject>Forkhead Transcription Factors - genetics</subject><subject>Forkhead Transcription Factors - immunology</subject><subject>Foxp3 protein</subject><subject>Gene Knock-In Techniques</subject><subject>Genetic regulation</subject><subject>Homeostasis</subject><subject>Immunoregulation</subject><subject>Immunotherapy</subject><subject>Interleukin 2</subject><subject>Interleukin-2 - genetics</subject><subject>Interleukin-2 - immunology</subject><subject>Interleukin-2 Receptor alpha Subunit - genetics</subject><subject>Interleukin-2 Receptor alpha Subunit - immunology</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Medicine</subject><subject>Melanoma</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>Physiological aspects</subject><subject>Studies</subject><subject>T-Lymphocytes, Regulatory - cytology</subject><subject>T-Lymphocytes, Regulatory - immunology</subject><subject>Transplants & implants</subject><subject>University graduates</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNkl1v0zAUhiMEYqPwDxBEQkJw0WL7OE5ygzRVDCoVTRoVt5Y_01Ru3MUJov8eh2ZTg3ZBcpHYfs57PvwmyWuMFhhy_Gnn-7YRbnHwjVkgTHHB6JPkEpdA5owgeHr2f5G8CGGHUAYFY8-TC8IyUmaYXCZw3Teqq31USr973TsxLFJv01tTDSvfHtNNujTOhVQe09V6Tl4mz6xwwbwav7Nkc_1ls_w2X998XS2v1nPFStLNgYGQ1Ba50QqUxFrmQsSkRAIGUVKicya1AW1lVuhcQy4AYZwVmSGMWpglb0-yB-cDH9sNHOekBCgZoEisToT2YscPbb0X7ZF7UfO_G76tuGi7WjnDlSqIyYpYmCmoQFJqYZEtM2BC2zwOapZ8HrP1ch8rNk3XCjcRnZ409ZZX_henLLZDWBT4MAq0_q43oeP7Oqg4N9EY3w91A2IFQbSI6Lt_0Me7G6lKxAbqxvqYVw2i_IoCZDQ-Q9rFI1R8tdnXKnrD1nF_EvBxEhCZzvzuKtGHwFc_bv-fvfk5Zd-fsVsjXLcN3vWDn8IUpCdQtT6E1tiHIWPEB2vfT4MP1uajtWPYm_MLegi69zL8AXHf8Wk</recordid><startdate>20151103</startdate><enddate>20151103</enddate><creator>Moon, Byung-In</creator><creator>Kim, Tae Hun</creator><creator>Seoh, Ju-Young</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>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20151103</creationdate><title>Functional Modulation of Regulatory T Cells by IL-2</title><author>Moon, Byung-In ; Kim, Tae Hun ; Seoh, Ju-Young</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-363ab4f87edc3cb1db7aa5122b313a942d76bde3dfb58d7d37a3011585e264f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Animals</topic><topic>Autocrine signalling</topic><topic>B cells</topic><topic>Biological markers</topic><topic>CD25 antigen</topic><topic>CD4 antigen</topic><topic>CD4 Antigens - genetics</topic><topic>CD4 Antigens - immunology</topic><topic>Cytokines</topic><topic>Diabetes</topic><topic>Drug dosages</topic><topic>Forkhead Transcription Factors - genetics</topic><topic>Forkhead Transcription Factors - immunology</topic><topic>Foxp3 protein</topic><topic>Gene Knock-In Techniques</topic><topic>Genetic regulation</topic><topic>Homeostasis</topic><topic>Immunoregulation</topic><topic>Immunotherapy</topic><topic>Interleukin 2</topic><topic>Interleukin-2 - genetics</topic><topic>Interleukin-2 - immunology</topic><topic>Interleukin-2 Receptor alpha Subunit - genetics</topic><topic>Interleukin-2 Receptor alpha Subunit - immunology</topic><topic>Lymphocytes</topic><topic>Lymphocytes T</topic><topic>Medicine</topic><topic>Melanoma</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>Physiological aspects</topic><topic>Studies</topic><topic>T-Lymphocytes, Regulatory - cytology</topic><topic>T-Lymphocytes, Regulatory - immunology</topic><topic>Transplants & implants</topic><topic>University graduates</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Moon, Byung-In</creatorcontrib><creatorcontrib>Kim, Tae Hun</creatorcontrib><creatorcontrib>Seoh, Ju-Young</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Moon, Byung-In</au><au>Kim, Tae Hun</au><au>Seoh, Ju-Young</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Functional Modulation of Regulatory T Cells by IL-2</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2015-11-03</date><risdate>2015</risdate><volume>10</volume><issue>11</issue><spage>e0141864</spage><epage>e0141864</epage><pages>e0141864-e0141864</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>The suppressive function of regulatory T cells (Tregs) is critical to the maintenance of immune homeostasis in vivo and yet, the specific identification of Tregs by phenotypic markers is not perfect. Tregs were originally identified in the CD4+CD25+ fraction of T cells, but FoxP3 expression was later included as an additional marker of Tregs as FoxP3 expression was identified as being critical to the development and function of these cells. Intracellular expression of FoxP3 makes it difficult in using to isolate live and not permeabilized cells for functional assays. As such CD4+CD25+ fraction is still frequently used for functional assays of Tregs. Although, the CD4+CD25+ fraction substantially overlaps with the FoxP3+ fraction, the minor mismatch between CD4+CD25+ and FoxP3+ fractions may confound the functional characteristics of Tregs. In this study, we isolated CD4+FoxP3+ as well as CD4+CD25+ fractions from Foxp3 knock-in mice, and compared their proliferative and suppressive activity in the presence or absence of various concentrations of IL-2. Our results showed comparable patterns of proliferative and suppressive responses for both fractions, except that contrary to the CD4+CD25+ fraction the FoxP3+ fraction did not proliferate in an autocrine fashion even in response to a strong stimulation. In presence of exogenous IL-2, both CD4+CD25+ and CD4+FoxP3+ fractions were more sensitive than the CD4+CD25- responder cells in proliferative responsiveness. In addition, a low dose IL-2 enhanced whereas a high dose abrogated the suppressive activities of the CD4+CD25+ and CD4+FoxP3+ fractions. These results may provide an additional understanding of the characteristics of the various fractions of isolated Tregs based on phenotype and function and the role of varying levels of exogenous IL-2 on the suppressive activity of these cells.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>26529512</pmid><doi>10.1371/journal.pone.0141864</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Autocrine signalling B cells Biological markers CD25 antigen CD4 antigen CD4 Antigens - genetics CD4 Antigens - immunology Cytokines Diabetes Drug dosages Forkhead Transcription Factors - genetics Forkhead Transcription Factors - immunology Foxp3 protein Gene Knock-In Techniques Genetic regulation Homeostasis Immunoregulation Immunotherapy Interleukin 2 Interleukin-2 - genetics Interleukin-2 - immunology Interleukin-2 Receptor alpha Subunit - genetics Interleukin-2 Receptor alpha Subunit - immunology Lymphocytes Lymphocytes T Medicine Melanoma Mice Mice, Transgenic Physiological aspects Studies T-Lymphocytes, Regulatory - cytology T-Lymphocytes, Regulatory - immunology Transplants & implants University graduates |
| title | Functional Modulation of Regulatory T Cells by IL-2 |
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