Impaired CD4 + T-cell proliferation and effector function correlates with repressive histone methylation events in a mouse model of severe sepsis
dc.contributor.author | Carson, William F. | en_US |
dc.contributor.author | Cavassani, Karen A. | en_US |
dc.contributor.author | Ito, Toshihiro | en_US |
dc.contributor.author | Schaller, Matthew A. | en_US |
dc.contributor.author | Ishii, Makoto | en_US |
dc.contributor.author | Dou, Yali | en_US |
dc.contributor.author | Kunkel, Steven L. | en_US |
dc.date.accessioned | 2010-05-07T18:06:59Z | |
dc.date.available | 2011-03-01T16:26:45Z | en_US |
dc.date.issued | 2010-04 | en_US |
dc.identifier.citation | Carson, William F.; Cavassani, Karen A.; Ito, Toshihiro; Schaller, Matthew; Ishii, Makoto; Dou, Yali; Kunkel, Steven L. (2010). "Impaired CD4 + T-cell proliferation and effector function correlates with repressive histone methylation events in a mouse model of severe sepsis." European Journal of Immunology 40(4): 998-1010. <http://hdl.handle.net/2027.42/71365> | en_US |
dc.identifier.issn | 0014-2980 | en_US |
dc.identifier.issn | 1521-4141 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/71365 | |
dc.description.abstract | Immunosuppression following severe sepsis remains a significant human health concern, as long-term morbidity and mortality rates of patients who have recovered from life-threatening septic shock remain poor. Mouse models of severe sepsis indicate this immunosuppression may be partly due to alterations in myeloid cell function; however, the effect of severe sepsis on subsequent CD4 + T-cell responses remains unclear. In the present study, CD4 + T cells from mice subjected to an experimental model of severe sepsis (cecal ligation and puncture (CLP)) were analyzed in vitro . CD4 + CD62L + T cells from CLP mice exhibited reduced proliferative capacity and altered gene expression. Additionally, CD4 + CD62L + T cells from CLP mice exhibit dysregulated cytokine production after in vitro skewing with exogenous cytokines, indicating a decreased capability of these cells to commit to either the T H 1 or T H 2 lineage. Repressive histone methylation marks were also evident at promoter regions for the T H 1 cytokine IFN-Γ and the T H 2 transcription factor GATA-3 in naÏve CD4 + T cells from CLP mice. These results provide evidence that CD4 + T-cell subsets from post-septic mice exhibit defects in activation and effector function, possibly due to chromatin remodeling proximal to genes involved in cytokine production or gene transcription. | en_US |
dc.format.extent | 407677 bytes | |
dc.format.extent | 3118 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.publisher | WILEY-VCH Verlag | en_US |
dc.subject.other | Life and Medical Sciences | en_US |
dc.subject.other | Microbiology and Immunology | en_US |
dc.title | Impaired CD4 + T-cell proliferation and effector function correlates with repressive histone methylation events in a mouse model of severe sepsis | en_US |
dc.type | Article | en_US |
dc.rights.robots | IndexNoFollow | en_US |
dc.subject.hlbsecondlevel | Biological Chemistry | en_US |
dc.subject.hlbsecondlevel | Public Health | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.subject.hlbtoplevel | Science | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | Department of Pathology, University of Michigan, Ann Arbor, MI, USA ; Department of Pathology, University of Michigan, 4710 BSRB, 109 Zina Pitcher Place, Ann Arbor, MI 48105, USA Fax: +1-734-615-0642 | en_US |
dc.contributor.affiliationum | Department of Pathology, University of Michigan, Ann Arbor, MI, USA | en_US |
dc.contributor.affiliationum | Department of Pathology, University of Michigan, Ann Arbor, MI, USA | en_US |
dc.contributor.affiliationum | Department of Pathology, University of Michigan, Ann Arbor, MI, USA | en_US |
dc.contributor.affiliationum | Department of Pathology, University of Michigan, Ann Arbor, MI, USA | en_US |
dc.contributor.affiliationum | Department of Pathology, University of Michigan, Ann Arbor, MI, USA | en_US |
dc.contributor.affiliationum | Department of Pathology, University of Michigan, Ann Arbor, MI, USA | en_US |
dc.identifier.pmid | 20127677 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/71365/1/998_ftp.pdf | |
dc.identifier.doi | 10.1002/eji.200939739 | en_US |
dc.identifier.source | European Journal of Immunology | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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