Leukemia inhibitory factor is produced by myelin-reactive T cells from multiple sclerosis patients and protects against tumor necrosis factor-α-induced oligodendrocyte apoptosis
In multiple sclerosis (MS), damage to oligodendrocytes is believed to be caused by an aberrant immune response initiated by autoreactive T cells. Increasing evidence indicates that these T cells are not exclusively detrimental but might also exert protective effects. We report for the first time tha...
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| Veröffentlicht in: | Journal of neuroscience research 2006-04, Vol.83 (5), p.763-774 |
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| creator | Vanderlocht, Joris Hellings, Niels Hendriks, Jerome J.A. Vandenabeele, Frank Moreels, Marjan Buntinx, Mieke Hoekstra, Dick Antel, Jack P. Stinissen, Piet |
| description | In multiple sclerosis (MS), damage to oligodendrocytes is believed to be caused by an aberrant immune response initiated by autoreactive T cells. Increasing evidence indicates that these T cells are not exclusively detrimental but might also exert protective effects. We report for the first time that myelin‐reactive T‐cell clones from eight MS patients (6/19) and five healthy controls (4/11) produce leukemia inhibitory factor (LIF), a member of the neuropoietic family of neurotrophins. In addition, T‐cell clones specific for tetanus toxoid, CD4+ and CD8+ T cells, and monocytes, but not B cells, secreted LIF. LIF‐producing T lymphocytes and macrophages were also identified immunohistochemically in both active and chronic‐active MS lesions. We further demonstrated dose‐dependent protective effects of LIF on tumor necrosis factor‐α‐induced apoptosis of oligodendrocytes. In conclusion, our data demonstrate that peripheral and CNS‐infiltrating T cells from MS patients produce LIF, a protective factor for oligodendrocytes. This study emphasizes that secretion of LIF may contribute to the neuroprotective effects of autoreactive T cells. © 2006 Wiley‐Liss, Inc. |
| doi_str_mv | 10.1002/jnr.20781 |
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Increasing evidence indicates that these T cells are not exclusively detrimental but might also exert protective effects. We report for the first time that myelin‐reactive T‐cell clones from eight MS patients (6/19) and five healthy controls (4/11) produce leukemia inhibitory factor (LIF), a member of the neuropoietic family of neurotrophins. In addition, T‐cell clones specific for tetanus toxoid, CD4+ and CD8+ T cells, and monocytes, but not B cells, secreted LIF. LIF‐producing T lymphocytes and macrophages were also identified immunohistochemically in both active and chronic‐active MS lesions. We further demonstrated dose‐dependent protective effects of LIF on tumor necrosis factor‐α‐induced apoptosis of oligodendrocytes. In conclusion, our data demonstrate that peripheral and CNS‐infiltrating T cells from MS patients produce LIF, a protective factor for oligodendrocytes. This study emphasizes that secretion of LIF may contribute to the neuroprotective effects of autoreactive T cells. © 2006 Wiley‐Liss, Inc.</description><identifier>ISSN: 0360-4012</identifier><identifier>EISSN: 1097-4547</identifier><identifier>DOI: 10.1002/jnr.20781</identifier><identifier>PMID: 16477612</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Animals ; Apoptosis - drug effects ; Apoptosis - immunology ; Brain - immunology ; Brain - metabolism ; Brain - pathology ; Ciliary Neurotrophic Factor - immunology ; Ciliary Neurotrophic Factor - metabolism ; Ciliary Neurotrophic Factor - pharmacology ; Cytokines - immunology ; Dose-Response Relationship, Drug ; Humans ; Immunohistochemistry ; Interleukin-6 - immunology ; Interleukin-6 - metabolism ; Interleukin-6 - pharmacology ; Leukemia Inhibitory Factor ; multiple sclerosis ; Multiple Sclerosis - immunology ; Multiple Sclerosis - physiopathology ; Myelin Sheath - immunology ; myelin-reactive T cells ; oligodendrocytes ; Oligodendroglia - drug effects ; Oligodendroglia - immunology ; Oligodendroglia - pathology ; Rats ; Reverse Transcriptase Polymerase Chain Reaction ; T-Lymphocytes - immunology ; T-Lymphocytes - metabolism ; Tumor Necrosis Factor-alpha - immunology ; Tumor Necrosis Factor-alpha - metabolism</subject><ispartof>Journal of neuroscience research, 2006-04, Vol.83 (5), p.763-774</ispartof><rights>Copyright © 2006 Wiley‐Liss, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3961-2a41dbf04a9d02b13ec0befd4eb91055caceadd70af78f06192df31a0fe27363</citedby><cites>FETCH-LOGICAL-c3961-2a41dbf04a9d02b13ec0befd4eb91055caceadd70af78f06192df31a0fe27363</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjnr.20781$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjnr.20781$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16477612$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Vanderlocht, Joris</creatorcontrib><creatorcontrib>Hellings, Niels</creatorcontrib><creatorcontrib>Hendriks, Jerome J.A.</creatorcontrib><creatorcontrib>Vandenabeele, Frank</creatorcontrib><creatorcontrib>Moreels, Marjan</creatorcontrib><creatorcontrib>Buntinx, Mieke</creatorcontrib><creatorcontrib>Hoekstra, Dick</creatorcontrib><creatorcontrib>Antel, Jack P.</creatorcontrib><creatorcontrib>Stinissen, Piet</creatorcontrib><title>Leukemia inhibitory factor is produced by myelin-reactive T cells from multiple sclerosis patients and protects against tumor necrosis factor-α-induced oligodendrocyte apoptosis</title><title>Journal of neuroscience research</title><addtitle>J. Neurosci. Res</addtitle><description>In multiple sclerosis (MS), damage to oligodendrocytes is believed to be caused by an aberrant immune response initiated by autoreactive T cells. Increasing evidence indicates that these T cells are not exclusively detrimental but might also exert protective effects. We report for the first time that myelin‐reactive T‐cell clones from eight MS patients (6/19) and five healthy controls (4/11) produce leukemia inhibitory factor (LIF), a member of the neuropoietic family of neurotrophins. In addition, T‐cell clones specific for tetanus toxoid, CD4+ and CD8+ T cells, and monocytes, but not B cells, secreted LIF. LIF‐producing T lymphocytes and macrophages were also identified immunohistochemically in both active and chronic‐active MS lesions. We further demonstrated dose‐dependent protective effects of LIF on tumor necrosis factor‐α‐induced apoptosis of oligodendrocytes. In conclusion, our data demonstrate that peripheral and CNS‐infiltrating T cells from MS patients produce LIF, a protective factor for oligodendrocytes. This study emphasizes that secretion of LIF may contribute to the neuroprotective effects of autoreactive T cells. © 2006 Wiley‐Liss, Inc.</description><subject>Animals</subject><subject>Apoptosis - drug effects</subject><subject>Apoptosis - immunology</subject><subject>Brain - immunology</subject><subject>Brain - metabolism</subject><subject>Brain - pathology</subject><subject>Ciliary Neurotrophic Factor - immunology</subject><subject>Ciliary Neurotrophic Factor - metabolism</subject><subject>Ciliary Neurotrophic Factor - pharmacology</subject><subject>Cytokines - immunology</subject><subject>Dose-Response Relationship, Drug</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Interleukin-6 - immunology</subject><subject>Interleukin-6 - metabolism</subject><subject>Interleukin-6 - pharmacology</subject><subject>Leukemia Inhibitory Factor</subject><subject>multiple sclerosis</subject><subject>Multiple Sclerosis - immunology</subject><subject>Multiple Sclerosis - physiopathology</subject><subject>Myelin Sheath - immunology</subject><subject>myelin-reactive T cells</subject><subject>oligodendrocytes</subject><subject>Oligodendroglia - drug effects</subject><subject>Oligodendroglia - immunology</subject><subject>Oligodendroglia - pathology</subject><subject>Rats</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>T-Lymphocytes - immunology</subject><subject>T-Lymphocytes - metabolism</subject><subject>Tumor Necrosis Factor-alpha - immunology</subject><subject>Tumor Necrosis Factor-alpha - metabolism</subject><issn>0360-4012</issn><issn>1097-4547</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kc1u1DAUhS0EokNhwQsgr5BYuLXjJJ4sUUUL1WiQ0EgsLce-Lm4TJ9gONI9VHoRnwiEDrFhdWf7OuT8HoZeMnjFKi_NbH84KKrbsEdow2ghSVqV4jDaU15SUlBUn6FmMt5TSpqn4U3TC6lKImhUb9GMH0x30TmHnv7jWpSHM2CqdK3YRj2EwkwaD2xn3M3TOkwD5130DfMAaui5iG4Ye91OX3NgBjrqDMMRFq5IDnyJW3ixGCfTyuFHOx4TT1OcWHvQKry3Jzwfi_Npx6NzNYMCbMOg5AVbjMKaFfY6eWNVFeHGsp-hw-e5w8Z7sPl59uHi7I5o3NSOFKplpLS1VY2jRMg6atmBNCW3DaFVppUEZI6iyYmtpzZrCWM4UtVAIXvNT9Hq1zaN_nSAm2bu4bKw8DFOUtcgnLLcsg29WcFklBrByDK5XYZaMyiUfmfORv_PJ7Kuj6dT2YP6Rx0AycL4C310H8_-d5PX-0x9LsipcTHD_V6HCXR6Ri0p-3l_JuuZNcX3ZyD3_BVrPsHE</recordid><startdate>200604</startdate><enddate>200604</enddate><creator>Vanderlocht, Joris</creator><creator>Hellings, Niels</creator><creator>Hendriks, Jerome J.A.</creator><creator>Vandenabeele, Frank</creator><creator>Moreels, Marjan</creator><creator>Buntinx, Mieke</creator><creator>Hoekstra, Dick</creator><creator>Antel, Jack P.</creator><creator>Stinissen, Piet</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><scope>BSCLL</scope><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>200604</creationdate><title>Leukemia inhibitory factor is produced by myelin-reactive T cells from multiple sclerosis patients and protects against tumor necrosis factor-α-induced oligodendrocyte apoptosis</title><author>Vanderlocht, Joris ; Hellings, Niels ; Hendriks, Jerome J.A. ; Vandenabeele, Frank ; Moreels, Marjan ; Buntinx, Mieke ; Hoekstra, Dick ; Antel, Jack P. ; Stinissen, Piet</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3961-2a41dbf04a9d02b13ec0befd4eb91055caceadd70af78f06192df31a0fe27363</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Animals</topic><topic>Apoptosis - drug effects</topic><topic>Apoptosis - immunology</topic><topic>Brain - immunology</topic><topic>Brain - metabolism</topic><topic>Brain - pathology</topic><topic>Ciliary Neurotrophic Factor - immunology</topic><topic>Ciliary Neurotrophic Factor - metabolism</topic><topic>Ciliary Neurotrophic Factor - pharmacology</topic><topic>Cytokines - immunology</topic><topic>Dose-Response Relationship, Drug</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Interleukin-6 - immunology</topic><topic>Interleukin-6 - metabolism</topic><topic>Interleukin-6 - pharmacology</topic><topic>Leukemia Inhibitory Factor</topic><topic>multiple sclerosis</topic><topic>Multiple Sclerosis - immunology</topic><topic>Multiple Sclerosis - physiopathology</topic><topic>Myelin Sheath - immunology</topic><topic>myelin-reactive T cells</topic><topic>oligodendrocytes</topic><topic>Oligodendroglia - drug effects</topic><topic>Oligodendroglia - immunology</topic><topic>Oligodendroglia - pathology</topic><topic>Rats</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>T-Lymphocytes - immunology</topic><topic>T-Lymphocytes - metabolism</topic><topic>Tumor Necrosis Factor-alpha - immunology</topic><topic>Tumor Necrosis Factor-alpha - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Vanderlocht, Joris</creatorcontrib><creatorcontrib>Hellings, Niels</creatorcontrib><creatorcontrib>Hendriks, Jerome J.A.</creatorcontrib><creatorcontrib>Vandenabeele, Frank</creatorcontrib><creatorcontrib>Moreels, Marjan</creatorcontrib><creatorcontrib>Buntinx, Mieke</creatorcontrib><creatorcontrib>Hoekstra, Dick</creatorcontrib><creatorcontrib>Antel, Jack P.</creatorcontrib><creatorcontrib>Stinissen, Piet</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of neuroscience research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Vanderlocht, Joris</au><au>Hellings, Niels</au><au>Hendriks, Jerome J.A.</au><au>Vandenabeele, Frank</au><au>Moreels, Marjan</au><au>Buntinx, Mieke</au><au>Hoekstra, Dick</au><au>Antel, Jack P.</au><au>Stinissen, Piet</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Leukemia inhibitory factor is produced by myelin-reactive T cells from multiple sclerosis patients and protects against tumor necrosis factor-α-induced oligodendrocyte apoptosis</atitle><jtitle>Journal of neuroscience research</jtitle><addtitle>J. Neurosci. Res</addtitle><date>2006-04</date><risdate>2006</risdate><volume>83</volume><issue>5</issue><spage>763</spage><epage>774</epage><pages>763-774</pages><issn>0360-4012</issn><eissn>1097-4547</eissn><abstract>In multiple sclerosis (MS), damage to oligodendrocytes is believed to be caused by an aberrant immune response initiated by autoreactive T cells. Increasing evidence indicates that these T cells are not exclusively detrimental but might also exert protective effects. We report for the first time that myelin‐reactive T‐cell clones from eight MS patients (6/19) and five healthy controls (4/11) produce leukemia inhibitory factor (LIF), a member of the neuropoietic family of neurotrophins. In addition, T‐cell clones specific for tetanus toxoid, CD4+ and CD8+ T cells, and monocytes, but not B cells, secreted LIF. LIF‐producing T lymphocytes and macrophages were also identified immunohistochemically in both active and chronic‐active MS lesions. We further demonstrated dose‐dependent protective effects of LIF on tumor necrosis factor‐α‐induced apoptosis of oligodendrocytes. In conclusion, our data demonstrate that peripheral and CNS‐infiltrating T cells from MS patients produce LIF, a protective factor for oligodendrocytes. This study emphasizes that secretion of LIF may contribute to the neuroprotective effects of autoreactive T cells. © 2006 Wiley‐Liss, Inc.</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>16477612</pmid><doi>10.1002/jnr.20781</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Apoptosis - drug effects Apoptosis - immunology Brain - immunology Brain - metabolism Brain - pathology Ciliary Neurotrophic Factor - immunology Ciliary Neurotrophic Factor - metabolism Ciliary Neurotrophic Factor - pharmacology Cytokines - immunology Dose-Response Relationship, Drug Humans Immunohistochemistry Interleukin-6 - immunology Interleukin-6 - metabolism Interleukin-6 - pharmacology Leukemia Inhibitory Factor multiple sclerosis Multiple Sclerosis - immunology Multiple Sclerosis - physiopathology Myelin Sheath - immunology myelin-reactive T cells oligodendrocytes Oligodendroglia - drug effects Oligodendroglia - immunology Oligodendroglia - pathology Rats Reverse Transcriptase Polymerase Chain Reaction T-Lymphocytes - immunology T-Lymphocytes - metabolism Tumor Necrosis Factor-alpha - immunology Tumor Necrosis Factor-alpha - metabolism |
| title | Leukemia inhibitory factor is produced by myelin-reactive T cells from multiple sclerosis patients and protects against tumor necrosis factor-α-induced oligodendrocyte apoptosis |
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