CD1d-expressing dendritic cells but not thymic epithelial cells can mediate negative selection of NKT cells
Natural killer T (NKT) cells are a unique immunoregulatory T cell population that is positively selected by CD1d-expressing thymocytes. Previous studies have shown that NKT cells exhibit autoreactivity, which raises the question of whether they are subject to negative selection. Here, we report that...
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| Veröffentlicht in: | The Journal of experimental medicine 2003-04, Vol.197 (7), p.907-918 |
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| container_title | The Journal of experimental medicine |
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| creator | Chun, Taehoon Page, Michael J Gapin, Laurent Matsuda, Jennifer L Xu, Honglin Nguyen, Hanh Kang, Hyung-Sik Stanic, Aleksandar K Joyce, Sebastian Koltun, Walter A Chorney, Michael J Kronenberg, Mitchell Wang, Chyung-Ru |
| description | Natural killer T (NKT) cells are a unique immunoregulatory T cell population that is positively selected by CD1d-expressing thymocytes. Previous studies have shown that NKT cells exhibit autoreactivity, which raises the question of whether they are subject to negative selection. Here, we report that the addition of agonist glycolipid alpha-galactosylceramide (alpha-GalCer) to a fetal thymic organ culture (FTOC) induces a dose-dependent disappearance of NKT cells, suggesting that NKT cells are susceptible to negative selection. Overexpression of CD1d in transgenic (Tg) mice results in reduced numbers of NKT cells, and the residual NKT cells in CD1d-Tg mice exhibit both an altered Vbeta usage and a reduced sensitivity to antigen. Furthermore, bone marrow (BM) chimeras between Tg and WT mice reveal that CD1d-expressing BM-derived dendritic cells, but not thymic epithelial cells, mediate the efficient negative selection of NKT cells. Thus, our data suggest that NKT cells developmentally undergo negative selection when engaged by high-avidity antigen or abundant self-antigen. |
| doi_str_mv | 10.1084/jem.20021366 |
| format | Article |
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Previous studies have shown that NKT cells exhibit autoreactivity, which raises the question of whether they are subject to negative selection. Here, we report that the addition of agonist glycolipid alpha-galactosylceramide (alpha-GalCer) to a fetal thymic organ culture (FTOC) induces a dose-dependent disappearance of NKT cells, suggesting that NKT cells are susceptible to negative selection. Overexpression of CD1d in transgenic (Tg) mice results in reduced numbers of NKT cells, and the residual NKT cells in CD1d-Tg mice exhibit both an altered Vbeta usage and a reduced sensitivity to antigen. Furthermore, bone marrow (BM) chimeras between Tg and WT mice reveal that CD1d-expressing BM-derived dendritic cells, but not thymic epithelial cells, mediate the efficient negative selection of NKT cells. Thus, our data suggest that NKT cells developmentally undergo negative selection when engaged by high-avidity antigen or abundant self-antigen.</description><identifier>ISSN: 0022-1007</identifier><identifier>EISSN: 1540-9538</identifier><identifier>DOI: 10.1084/jem.20021366</identifier><identifier>PMID: 12682110</identifier><language>eng</language><publisher>United States: The Rockefeller University Press</publisher><subject>Animals ; Antigens, CD1 - physiology ; Antigens, CD1d ; Bone Marrow Cells - physiology ; Dendritic Cells - physiology ; Epithelial Cells - physiology ; Galactosylceramides - pharmacology ; Killer Cells, Natural - physiology ; Lymphocyte Activation ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Organ Culture Techniques ; Receptors, Antigen, T-Cell, alpha-beta - physiology ; Stromal Cells - physiology ; Thymus Gland - cytology</subject><ispartof>The Journal of experimental medicine, 2003-04, Vol.197 (7), p.907-918</ispartof><rights>Copyright © 2003, The Rockefeller University Press</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c411t-6527a878214f4b77d2783a5320d5b4f6169a4075a90442c3d1783c2ec45dfbb53</citedby><cites>FETCH-LOGICAL-c411t-6527a878214f4b77d2783a5320d5b4f6169a4075a90442c3d1783c2ec45dfbb53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12682110$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chun, Taehoon</creatorcontrib><creatorcontrib>Page, Michael J</creatorcontrib><creatorcontrib>Gapin, Laurent</creatorcontrib><creatorcontrib>Matsuda, Jennifer L</creatorcontrib><creatorcontrib>Xu, Honglin</creatorcontrib><creatorcontrib>Nguyen, Hanh</creatorcontrib><creatorcontrib>Kang, Hyung-Sik</creatorcontrib><creatorcontrib>Stanic, Aleksandar K</creatorcontrib><creatorcontrib>Joyce, Sebastian</creatorcontrib><creatorcontrib>Koltun, Walter A</creatorcontrib><creatorcontrib>Chorney, Michael J</creatorcontrib><creatorcontrib>Kronenberg, Mitchell</creatorcontrib><creatorcontrib>Wang, Chyung-Ru</creatorcontrib><title>CD1d-expressing dendritic cells but not thymic epithelial cells can mediate negative selection of NKT cells</title><title>The Journal of experimental medicine</title><addtitle>J Exp Med</addtitle><description>Natural killer T (NKT) cells are a unique immunoregulatory T cell population that is positively selected by CD1d-expressing thymocytes. Previous studies have shown that NKT cells exhibit autoreactivity, which raises the question of whether they are subject to negative selection. Here, we report that the addition of agonist glycolipid alpha-galactosylceramide (alpha-GalCer) to a fetal thymic organ culture (FTOC) induces a dose-dependent disappearance of NKT cells, suggesting that NKT cells are susceptible to negative selection. Overexpression of CD1d in transgenic (Tg) mice results in reduced numbers of NKT cells, and the residual NKT cells in CD1d-Tg mice exhibit both an altered Vbeta usage and a reduced sensitivity to antigen. Furthermore, bone marrow (BM) chimeras between Tg and WT mice reveal that CD1d-expressing BM-derived dendritic cells, but not thymic epithelial cells, mediate the efficient negative selection of NKT cells. Thus, our data suggest that NKT cells developmentally undergo negative selection when engaged by high-avidity antigen or abundant self-antigen.</description><subject>Animals</subject><subject>Antigens, CD1 - physiology</subject><subject>Antigens, CD1d</subject><subject>Bone Marrow Cells - physiology</subject><subject>Dendritic Cells - physiology</subject><subject>Epithelial Cells - physiology</subject><subject>Galactosylceramides - pharmacology</subject><subject>Killer Cells, Natural - physiology</subject><subject>Lymphocyte Activation</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Transgenic</subject><subject>Organ Culture Techniques</subject><subject>Receptors, Antigen, T-Cell, alpha-beta - physiology</subject><subject>Stromal Cells - physiology</subject><subject>Thymus Gland - cytology</subject><issn>0022-1007</issn><issn>1540-9538</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc1P3DAUxK0KBAvl1jPyiVMDfv6InUulagstAsGFni3Hedk1TZxt7EXlvyer3dJy4vSkmZ9G8zSEfAJ2DszIi0fszzljHERZfiAzUJIVlRJmj8wmlRfAmD4kRyk9MgZSqvKAHAIvDQdgM_Jr_g2aAv-sRkwpxAVtMDZjyMFTj12XaL3ONA6Z5uVzP4m4CnmJXXDdzvcu0h6b4DLSiAuXwxPShB36HIZIh5be3Txs2Y9kv3VdwpPdPSY_ry4f5j-K2_vv1_Ovt4WXALkoFdfO6KmgbGWtdcO1EU4JzhpVy7aEsnKSaeUqJiX3ooHJ9xy9VE1b10ocky_b3NW6nqp5jHl0nV2NoXfjsx1csG-dGJZ2MTxZDpUw1SbgbBcwDr_XmLLtQ9q84CIO62S1AFMagHdBMFoZIdkEft6CfhxSGrF9bQPMbma004z274wTfvr_B__g3W7iBQ41mVI</recordid><startdate>20030407</startdate><enddate>20030407</enddate><creator>Chun, Taehoon</creator><creator>Page, Michael J</creator><creator>Gapin, Laurent</creator><creator>Matsuda, Jennifer L</creator><creator>Xu, Honglin</creator><creator>Nguyen, Hanh</creator><creator>Kang, Hyung-Sik</creator><creator>Stanic, Aleksandar K</creator><creator>Joyce, Sebastian</creator><creator>Koltun, Walter A</creator><creator>Chorney, Michael J</creator><creator>Kronenberg, Mitchell</creator><creator>Wang, Chyung-Ru</creator><general>The Rockefeller University Press</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><scope>5PM</scope></search><sort><creationdate>20030407</creationdate><title>CD1d-expressing dendritic cells but not thymic epithelial cells can mediate negative selection of NKT cells</title><author>Chun, Taehoon ; 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Previous studies have shown that NKT cells exhibit autoreactivity, which raises the question of whether they are subject to negative selection. Here, we report that the addition of agonist glycolipid alpha-galactosylceramide (alpha-GalCer) to a fetal thymic organ culture (FTOC) induces a dose-dependent disappearance of NKT cells, suggesting that NKT cells are susceptible to negative selection. Overexpression of CD1d in transgenic (Tg) mice results in reduced numbers of NKT cells, and the residual NKT cells in CD1d-Tg mice exhibit both an altered Vbeta usage and a reduced sensitivity to antigen. Furthermore, bone marrow (BM) chimeras between Tg and WT mice reveal that CD1d-expressing BM-derived dendritic cells, but not thymic epithelial cells, mediate the efficient negative selection of NKT cells. 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| subjects | Animals Antigens, CD1 - physiology Antigens, CD1d Bone Marrow Cells - physiology Dendritic Cells - physiology Epithelial Cells - physiology Galactosylceramides - pharmacology Killer Cells, Natural - physiology Lymphocyte Activation Mice Mice, Inbred C57BL Mice, Transgenic Organ Culture Techniques Receptors, Antigen, T-Cell, alpha-beta - physiology Stromal Cells - physiology Thymus Gland - cytology |
| title | CD1d-expressing dendritic cells but not thymic epithelial cells can mediate negative selection of NKT cells |
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