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dc.contributor.authorZhan, YF
dc.contributor.authorFunda, DP
dc.contributor.authorEvery, AL
dc.contributor.authorFundova, P
dc.contributor.authorPurton, JF
dc.contributor.authorLiddicoat, DR
dc.contributor.authorCole, TJ
dc.contributor.authorGodfrey, DI
dc.contributor.authorBrady, JL
dc.contributor.authorMannering, SI
dc.contributor.authorHarrison, LC
dc.contributor.authorLew, AM
dc.date.available2014-05-21T19:30:49Z
dc.date.issued2004-09-01
dc.identifierpii: dxh134
dc.identifier.citationZhan, Y. F., Funda, D. P., Every, A. L., Fundova, P., Purton, J. F., Liddicoat, D. R., Cole, T. J., Godfrey, D. I., Brady, J. L., Mannering, S. I., Harrison, L. C. & Lew, A. M. (2004). TCR-mediated activation promotes GITR upregulation in T cells and resistance to glucocorticoid-induced death. INTERNATIONAL IMMUNOLOGY, 16 (9), pp.1315-1321. https://doi.org/10.1093/intimm/dxh134.
dc.identifier.issn0953-8178
dc.identifier.urihttp://hdl.handle.net/11343/26392
dc.descriptionC1 - Journal Articles Refereed
dc.description.abstractT lymphocytes (pivotal in many inflammatory pathologies) are targets for glucocorticoid hormone (GC). How TCR-mediated activation and GC signaling via glucocorticoid receptor (GR) impact on T-cell fates is not fully defined. We delineated here the expression of a recently identified glucocorticoid-induced TNF receptor (GITR) induced by GC and by TCR-mediated T-cell activation in GC receptor (GR)-deficient mice (GR-/-). We also compared the action of GC on GITR+ and GITR- T cells by monitoring apoptosis, proliferation and cytokine production stimulated by anti-CD3 antibody. By using GR-/- mice, we observed that the development of GITR+ T cells (both in thymus and periphery) is not dependent upon GR signaling. This contradicts the implication of GITR's name reflecting GC induction. TCR-mediated T-cell activation induced GITR expression in both GR+/+ and GR-/- cells. Somewhat unexpectedly, there was very modest GITR upregulation on GR+/+ T cells by a range of GC doses (10(-8) to 10(-6) M). Constitutive expression of GITR by a subset of CD4+ cells did not significantly render them resistant to GC-induced cell death. However, TCR-induced GITR upregulation on GR+/+ T cells was correlated with resistance to GC-mediated apoptosis suggesting that GITR, in conjunction with other (as yet unidentified) TCR-induced factors, protects T cells from apoptosis. Thus, even though GC is a potent inducer of apoptosis of T cells, activated T cells are resistant to GC-mediated killing. Meanwhile, although GC suppressed anti-CD3-induced cytokine production, cell proliferation was unaffected by GC in GR+/+ mice. GR deficiency has no effect on anti-CD3-induced cytokine production and proliferation. Our findings also have implications for GC treatment in that it would be more difficult to abrogate an ongoing T-cell mediated inflammatory response than to prevent its induction.
dc.formatapplication/pdf
dc.languageEnglish
dc.publisherOXFORD UNIV PRESS
dc.subjectCellular Immunology; Immune System and Allergy
dc.titleTCR-mediated activation promotes GITR upregulation in T cells and resistance to glucocorticoid-induced death
dc.typeJournal Article
dc.identifier.doi10.1093/intimm/dxh134
melbourne.peerreviewPeer Reviewed
melbourne.affiliationThe University of Melbourne
melbourne.affiliation.departmentMicrobiology And Immunology
melbourne.source.titleINTERNATIONAL IMMUNOLOGY
melbourne.source.volume16
melbourne.source.issue9
melbourne.source.pages1315-1321
dc.research.coderfcd320202
dc.research.codeseo1998730102
melbourne.publicationid32030
melbourne.elementsid265938
melbourne.contributor.authorEvery, Alison
melbourne.contributor.authorLIDDICOAT, DOUGLAS
melbourne.contributor.authorGodfrey, Dale
melbourne.contributor.authorMannering, Stuart
melbourne.contributor.authorBrady, Jamie
melbourne.contributor.authorLew, Andrew
melbourne.contributor.authorHarrison, Leonard
melbourne.contributor.authorZhan, Yifan
melbourne.contributor.authorPURTON, JARED
melbourne.contributor.authorCOLE, TIMOTHY
dc.identifier.eissn1460-2377
melbourne.accessrightsThis item is currently not available from this repository


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