Ox40 regulates the conversion and suppressive function of double-negative regulatory T cells
Naïve CD4 T cells can be converted to double-negative regulatory T cells (DNT) by mature dendritic cells (mDCs) and IL-2 stimulation, with IL-2 enhancing the proliferation and Perforin expression of DNT. However, the molecules that affect the conversion of DNT are still not clear. Here, we investiga...
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| Veröffentlicht in: | International immunopharmacology 2018-12, Vol.65, p.16-22 |
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| creator | Liu, Kai Ye, Huichu Zhou, Jin Tian, Yue Xu, Hufeng Sun, Xuelian Zhang, Dong |
| description | Naïve CD4 T cells can be converted to double-negative regulatory T cells (DNT) by mature dendritic cells (mDCs) and IL-2 stimulation, with IL-2 enhancing the proliferation and Perforin expression of DNT. However, the molecules that affect the conversion of DNT are still not clear. Here, we investigated the effects of Ox40 on the conversion and function of DNT in vitro and in vivo without IL-2. We found that OX86 (an Ox40 agonist) increased the conversion rate of DNT but failed to enhance the suppressive function of DNT. Ox40 deficiency profoundly decreased the conversion rate and suppressive function of DNT. This suppression decline was caused by effects of Ox40 on proliferation and apoptosis independent of Perforin, Granzyme B and Fas ligand. Ox40 deficiency influenced the regulatory function of DNT through multiple signals, such as Cxcr3, Cd160 and Cd30, independently of Prf, Gzmb and Fasl. In conclusion, we elucidated that Ox40 promotes the conversion and maintenance of DNT. Ox40 deficiency reduced the regulatory function of DNT both in vitro and in vivo by regulating proliferation, apoptosis, and suppression-related genes.
•Ox40 but not CD28 or CD154 deficiency profoundly decreased conversion rate of DN Tregs from CD4 T cells.•Ox40 deficiency markedly decreased the suppressive function of DN Tregs.•Ox40 affected DN Tregs' suppressive function by survival and gene expression independently of Prf, Gzmb and Fasl. |
| doi_str_mv | 10.1016/j.intimp.2018.09.035 |
| format | Article |
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•Ox40 but not CD28 or CD154 deficiency profoundly decreased conversion rate of DN Tregs from CD4 T cells.•Ox40 deficiency markedly decreased the suppressive function of DN Tregs.•Ox40 affected DN Tregs' suppressive function by survival and gene expression independently of Prf, Gzmb and Fasl.</description><identifier>ISSN: 1567-5769</identifier><identifier>EISSN: 1878-1705</identifier><identifier>DOI: 10.1016/j.intimp.2018.09.035</identifier><identifier>PMID: 30268799</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Animals ; Antibodies, Monoclonal ; Apoptosis ; Apoptosis - physiology ; CD160 ; CD30 ; CD30 antigen ; CD4 antigen ; Cell growth ; Cell Proliferation ; Conversion ; CXCR3 ; CXCR3 protein ; Dendritic cells ; Double negative T cells ; Down-regulation ; FasL protein ; Gene Expression Regulation - drug effects ; Granzyme B ; Immunoregulation ; Interleukin 2 ; Lymphocytes ; Lymphocytes T ; Membrane Glycoproteins - genetics ; Membrane Glycoproteins - metabolism ; Mice ; Mice, Inbred Strains ; Mice, Knockout ; Ox40 ; Perforin ; T cell receptors ; T-Lymphocytes, Regulatory - classification ; T-Lymphocytes, Regulatory - drug effects ; T-Lymphocytes, Regulatory - metabolism ; Tumor Necrosis Factors - genetics ; Tumor Necrosis Factors - metabolism</subject><ispartof>International immunopharmacology, 2018-12, Vol.65, p.16-22</ispartof><rights>2018</rights><rights>Copyright © 2018. Published by Elsevier B.V.</rights><rights>Copyright Elsevier BV Dec 2018</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c390t-9c706c6ffc372c83ae4924c9e7be639b1932f0905b889b903f3a123852e0e78a3</citedby><cites>FETCH-LOGICAL-c390t-9c706c6ffc372c83ae4924c9e7be639b1932f0905b889b903f3a123852e0e78a3</cites><orcidid>0000-0002-3404-5173</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1567576918307343$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30268799$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Liu, Kai</creatorcontrib><creatorcontrib>Ye, Huichu</creatorcontrib><creatorcontrib>Zhou, Jin</creatorcontrib><creatorcontrib>Tian, Yue</creatorcontrib><creatorcontrib>Xu, Hufeng</creatorcontrib><creatorcontrib>Sun, Xuelian</creatorcontrib><creatorcontrib>Zhang, Dong</creatorcontrib><title>Ox40 regulates the conversion and suppressive function of double-negative regulatory T cells</title><title>International immunopharmacology</title><addtitle>Int Immunopharmacol</addtitle><description>Naïve CD4 T cells can be converted to double-negative regulatory T cells (DNT) by mature dendritic cells (mDCs) and IL-2 stimulation, with IL-2 enhancing the proliferation and Perforin expression of DNT. However, the molecules that affect the conversion of DNT are still not clear. Here, we investigated the effects of Ox40 on the conversion and function of DNT in vitro and in vivo without IL-2. We found that OX86 (an Ox40 agonist) increased the conversion rate of DNT but failed to enhance the suppressive function of DNT. Ox40 deficiency profoundly decreased the conversion rate and suppressive function of DNT. This suppression decline was caused by effects of Ox40 on proliferation and apoptosis independent of Perforin, Granzyme B and Fas ligand. Ox40 deficiency influenced the regulatory function of DNT through multiple signals, such as Cxcr3, Cd160 and Cd30, independently of Prf, Gzmb and Fasl. In conclusion, we elucidated that Ox40 promotes the conversion and maintenance of DNT. Ox40 deficiency reduced the regulatory function of DNT both in vitro and in vivo by regulating proliferation, apoptosis, and suppression-related genes.
•Ox40 but not CD28 or CD154 deficiency profoundly decreased conversion rate of DN Tregs from CD4 T cells.•Ox40 deficiency markedly decreased the suppressive function of DN Tregs.•Ox40 affected DN Tregs' suppressive function by survival and gene expression independently of Prf, Gzmb and Fasl.</description><subject>Animals</subject><subject>Antibodies, Monoclonal</subject><subject>Apoptosis</subject><subject>Apoptosis - physiology</subject><subject>CD160</subject><subject>CD30</subject><subject>CD30 antigen</subject><subject>CD4 antigen</subject><subject>Cell growth</subject><subject>Cell Proliferation</subject><subject>Conversion</subject><subject>CXCR3</subject><subject>CXCR3 protein</subject><subject>Dendritic cells</subject><subject>Double negative T cells</subject><subject>Down-regulation</subject><subject>FasL protein</subject><subject>Gene Expression Regulation - drug effects</subject><subject>Granzyme B</subject><subject>Immunoregulation</subject><subject>Interleukin 2</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Membrane Glycoproteins - genetics</subject><subject>Membrane Glycoproteins - metabolism</subject><subject>Mice</subject><subject>Mice, Inbred Strains</subject><subject>Mice, Knockout</subject><subject>Ox40</subject><subject>Perforin</subject><subject>T cell receptors</subject><subject>T-Lymphocytes, Regulatory - classification</subject><subject>T-Lymphocytes, Regulatory - drug effects</subject><subject>T-Lymphocytes, Regulatory - metabolism</subject><subject>Tumor Necrosis Factors - genetics</subject><subject>Tumor Necrosis Factors - metabolism</subject><issn>1567-5769</issn><issn>1878-1705</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1v1DAQhi0Eou3CP0DIEhcuCWM78ccFCVVAkSr1Um5IluNMilfZONjJqv33ONqFAwdOY80883r0EPKGQc2AyQ_7OkxLOMw1B6ZrMDWI9hm5ZFrpiilon5d3K1XVKmkuyFXOe4DSb9hLciGAS62MuSQ_7h4boAkf1tEtmOnyE6mP0xFTDnGibuppXuc5Yc7hiHRYJ79sgzjQPq7diNWED27ZZueQmJ7oPfU4jvkVeTG4MePrc92R718-31_fVLd3X79df7qtvDCwVMYrkF4OgxeKey0cNoY33qDqUArTMSP4AAbaTmvTGRCDcIwL3XIEVNqJHXl_yp1T_LViXuwh5O0CN2Fcs-WMtVxpDqqg7_5B93FNU7muUFKCbliJ3pHmRPkUc0442DmFg0tPloHd7Nu9Pdm3m30Lxhb7Ze3tOXztDtj_XfqjuwAfTwAWG8eAyWYfcPLYh4R-sX0M___hN5vbl6E</recordid><startdate>201812</startdate><enddate>201812</enddate><creator>Liu, Kai</creator><creator>Ye, Huichu</creator><creator>Zhou, Jin</creator><creator>Tian, Yue</creator><creator>Xu, Hufeng</creator><creator>Sun, Xuelian</creator><creator>Zhang, Dong</creator><general>Elsevier B.V</general><general>Elsevier BV</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>7QO</scope><scope>7T5</scope><scope>7U7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-3404-5173</orcidid></search><sort><creationdate>201812</creationdate><title>Ox40 regulates the conversion and suppressive function of double-negative regulatory T cells</title><author>Liu, Kai ; Ye, Huichu ; Zhou, Jin ; Tian, Yue ; Xu, Hufeng ; Sun, Xuelian ; Zhang, Dong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c390t-9c706c6ffc372c83ae4924c9e7be639b1932f0905b889b903f3a123852e0e78a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Animals</topic><topic>Antibodies, Monoclonal</topic><topic>Apoptosis</topic><topic>Apoptosis - physiology</topic><topic>CD160</topic><topic>CD30</topic><topic>CD30 antigen</topic><topic>CD4 antigen</topic><topic>Cell growth</topic><topic>Cell Proliferation</topic><topic>Conversion</topic><topic>CXCR3</topic><topic>CXCR3 protein</topic><topic>Dendritic cells</topic><topic>Double negative T cells</topic><topic>Down-regulation</topic><topic>FasL protein</topic><topic>Gene Expression Regulation - drug effects</topic><topic>Granzyme B</topic><topic>Immunoregulation</topic><topic>Interleukin 2</topic><topic>Lymphocytes</topic><topic>Lymphocytes T</topic><topic>Membrane Glycoproteins - genetics</topic><topic>Membrane Glycoproteins - metabolism</topic><topic>Mice</topic><topic>Mice, Inbred Strains</topic><topic>Mice, Knockout</topic><topic>Ox40</topic><topic>Perforin</topic><topic>T cell receptors</topic><topic>T-Lymphocytes, Regulatory - classification</topic><topic>T-Lymphocytes, Regulatory - drug effects</topic><topic>T-Lymphocytes, Regulatory - metabolism</topic><topic>Tumor Necrosis Factors - genetics</topic><topic>Tumor Necrosis Factors - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Liu, Kai</creatorcontrib><creatorcontrib>Ye, Huichu</creatorcontrib><creatorcontrib>Zhou, Jin</creatorcontrib><creatorcontrib>Tian, Yue</creatorcontrib><creatorcontrib>Xu, Hufeng</creatorcontrib><creatorcontrib>Sun, Xuelian</creatorcontrib><creatorcontrib>Zhang, Dong</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Immunology Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>International immunopharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Liu, Kai</au><au>Ye, Huichu</au><au>Zhou, Jin</au><au>Tian, Yue</au><au>Xu, Hufeng</au><au>Sun, Xuelian</au><au>Zhang, Dong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Ox40 regulates the conversion and suppressive function of double-negative regulatory T cells</atitle><jtitle>International immunopharmacology</jtitle><addtitle>Int Immunopharmacol</addtitle><date>2018-12</date><risdate>2018</risdate><volume>65</volume><spage>16</spage><epage>22</epage><pages>16-22</pages><issn>1567-5769</issn><eissn>1878-1705</eissn><abstract>Naïve CD4 T cells can be converted to double-negative regulatory T cells (DNT) by mature dendritic cells (mDCs) and IL-2 stimulation, with IL-2 enhancing the proliferation and Perforin expression of DNT. However, the molecules that affect the conversion of DNT are still not clear. Here, we investigated the effects of Ox40 on the conversion and function of DNT in vitro and in vivo without IL-2. We found that OX86 (an Ox40 agonist) increased the conversion rate of DNT but failed to enhance the suppressive function of DNT. Ox40 deficiency profoundly decreased the conversion rate and suppressive function of DNT. This suppression decline was caused by effects of Ox40 on proliferation and apoptosis independent of Perforin, Granzyme B and Fas ligand. Ox40 deficiency influenced the regulatory function of DNT through multiple signals, such as Cxcr3, Cd160 and Cd30, independently of Prf, Gzmb and Fasl. In conclusion, we elucidated that Ox40 promotes the conversion and maintenance of DNT. Ox40 deficiency reduced the regulatory function of DNT both in vitro and in vivo by regulating proliferation, apoptosis, and suppression-related genes.
•Ox40 but not CD28 or CD154 deficiency profoundly decreased conversion rate of DN Tregs from CD4 T cells.•Ox40 deficiency markedly decreased the suppressive function of DN Tregs.•Ox40 affected DN Tregs' suppressive function by survival and gene expression independently of Prf, Gzmb and Fasl.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>30268799</pmid><doi>10.1016/j.intimp.2018.09.035</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0002-3404-5173</orcidid></addata></record> |
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| subjects | Animals Antibodies, Monoclonal Apoptosis Apoptosis - physiology CD160 CD30 CD30 antigen CD4 antigen Cell growth Cell Proliferation Conversion CXCR3 CXCR3 protein Dendritic cells Double negative T cells Down-regulation FasL protein Gene Expression Regulation - drug effects Granzyme B Immunoregulation Interleukin 2 Lymphocytes Lymphocytes T Membrane Glycoproteins - genetics Membrane Glycoproteins - metabolism Mice Mice, Inbred Strains Mice, Knockout Ox40 Perforin T cell receptors T-Lymphocytes, Regulatory - classification T-Lymphocytes, Regulatory - drug effects T-Lymphocytes, Regulatory - metabolism Tumor Necrosis Factors - genetics Tumor Necrosis Factors - metabolism |
| title | Ox40 regulates the conversion and suppressive function of double-negative regulatory T cells |
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