File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: The interferon regulatory transcription factor IRF-1 controls positive and negative selection of CD8+ thymocytes

TitleThe interferon regulatory transcription factor IRF-1 controls positive and negative selection of CD8<sup>+</sup> thymocytes
Authors
Issue Date1997
Citation
Immunity, 1997, v. 7, n. 2, p. 243-254 How to Cite?
AbstractLittle is known about the molecular mechanisms and transcriptional regulation that govern T cell selection processes and the differentiation of CD4+ and CD8+ T cells. Mice lacking the interferon regulatory transcription factor-1 (IRF-1) have reduced numbers of mature CD8+ cells within the thymus and peripheral lymphatic organs. Here we show that positive and negative T cell selection of two MHC class I-restricted TCRαβ transgenes, H-Y and P14, are impaired in IRF-1(-/-) mice. The absence of IRF-1 resulted in decreased expression of LMP2, TAP1, and MHC class I on thymic stromal cells. Despite decreased MHC class I expression on IRF-1(-/- ) thymic stromal cells, the defect in CD8+ T cells development did not reside in the thymic environment, and IRF-1(-/-) stromal cells can fully support development of CD8+ thymocytes in in vivo bone marrow chimeras and in vitro reaggregation cultures. Moreover, IRF-1(-/-) thymocytes displayed impaired TCR-mediated signal transduction, and the induction of negative selection in TCR Tg thymocytes from IRF-1(-/-) mice required a 1000-fold increase in selecting peptide. We also provide evidence that IRF-1 is mainly expressed in mature, but not immature, thymocytes and that expression of IRF-1 in immature thymocytes is induced after peptide-specific TCR activation. These results indicate that IRF-1 regulates gene expression in developing thymocytes required for lineage commitment and selection of CD8+ thymocytes.
Persistent Identifierhttp://hdl.handle.net/10722/291404
ISSN
2023 Impact Factor: 25.5
2023 SCImago Journal Rankings: 13.578
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorPenninger, Josef M.-
dc.contributor.authorSirard, Christian-
dc.contributor.authorMittrücker, Hans Willi-
dc.contributor.authorChidgey, Anne-
dc.contributor.authorKozieradzki, Ivona-
dc.contributor.authorNghiem, Mai-
dc.contributor.authorHakem, Anne-
dc.contributor.authorKimura, Tohru-
dc.contributor.authorTimms, Emma-
dc.contributor.authorBoyd, Richard-
dc.contributor.authorTaniguchi, Tadatsugu-
dc.contributor.authorMatsuyama, Toshifumi-
dc.contributor.authorMak, Tak W.-
dc.date.accessioned2020-11-17T14:54:17Z-
dc.date.available2020-11-17T14:54:17Z-
dc.date.issued1997-
dc.identifier.citationImmunity, 1997, v. 7, n. 2, p. 243-254-
dc.identifier.issn1074-7613-
dc.identifier.urihttp://hdl.handle.net/10722/291404-
dc.description.abstractLittle is known about the molecular mechanisms and transcriptional regulation that govern T cell selection processes and the differentiation of CD4+ and CD8+ T cells. Mice lacking the interferon regulatory transcription factor-1 (IRF-1) have reduced numbers of mature CD8+ cells within the thymus and peripheral lymphatic organs. Here we show that positive and negative T cell selection of two MHC class I-restricted TCRαβ transgenes, H-Y and P14, are impaired in IRF-1(-/-) mice. The absence of IRF-1 resulted in decreased expression of LMP2, TAP1, and MHC class I on thymic stromal cells. Despite decreased MHC class I expression on IRF-1(-/- ) thymic stromal cells, the defect in CD8+ T cells development did not reside in the thymic environment, and IRF-1(-/-) stromal cells can fully support development of CD8+ thymocytes in in vivo bone marrow chimeras and in vitro reaggregation cultures. Moreover, IRF-1(-/-) thymocytes displayed impaired TCR-mediated signal transduction, and the induction of negative selection in TCR Tg thymocytes from IRF-1(-/-) mice required a 1000-fold increase in selecting peptide. We also provide evidence that IRF-1 is mainly expressed in mature, but not immature, thymocytes and that expression of IRF-1 in immature thymocytes is induced after peptide-specific TCR activation. These results indicate that IRF-1 regulates gene expression in developing thymocytes required for lineage commitment and selection of CD8+ thymocytes.-
dc.languageeng-
dc.relation.ispartofImmunity-
dc.titleThe interferon regulatory transcription factor IRF-1 controls positive and negative selection of CD8<sup>+</sup> thymocytes-
dc.typeArticle-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1016/S1074-7613(00)80527-0-
dc.identifier.pmid9285409-
dc.identifier.scopuseid_2-s2.0-0030820417-
dc.identifier.volume7-
dc.identifier.issue2-
dc.identifier.spage243-
dc.identifier.epage254-
dc.identifier.isiWOS:A1997XT49200008-
dc.identifier.issnl1074-7613-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats