rdf:type |
|
lifeskim:mentions |
umls-concept:C0021469,
umls-concept:C0035820,
umls-concept:C0039194,
umls-concept:C0205314,
umls-concept:C0220905,
umls-concept:C0441655,
umls-concept:C0679622,
umls-concept:C1332714,
umls-concept:C1334114,
umls-concept:C1420810,
umls-concept:C1420812,
umls-concept:C1533157,
umls-concept:C1707455
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pubmed:issue |
7
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pubmed:dateCreated |
2005-3-22
|
pubmed:abstractText |
OX40 (CD134) is a member of the tumor necrosis factor (TNF) receptor family that is transiently expressed on T cells after T-cell receptor (TCR) ligation. Both naive and activated CD4(+)CD25+ regulatory T cells (T reg's) express OX40 but its functional role has not been determined. Since glucocorticoid-induced tumor necrosis factor receptor (GITR), a related TNF receptor family member, influences T reg function, we tested whether OX40 might have similar effect. Triggering either GITR or OX40 on T reg's using agonist antibodies inhibited their capacity to suppress and restored effector T-cell proliferation, interleukin-2 (IL-2) gene transcription and cytokine production. OX40 abrogation of T reg suppression was confirmed in vivo in a model of graft-versus-host disease (GVHD). In a fully allogeneic C57BL/6>BALB/c bone marrow transplantation, GVHD was lethal unless T reg's were cotransferred with the bone marrow and effector T cells. Strikingly, T reg suppression of GVHD was abrogated either by intraperitoneal injection of anti-OX40 or anti-GITR monoclonal antibodies (mAbs) immediately after transfer, or by in vitro pretreatment of T reg's with the same mAbs before transfer. Cumulatively, the results suggest that in addition to controlling memory T-cell numbers, OX40 directly controls T reg-mediated suppression.
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pubmed:language |
eng
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pubmed:journal |
|
pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Monoclonal,
http://linkedlifedata.com/resource/pubmed/chemical/Glucocorticoid-Induced...,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-2,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Interleukin-2,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Nerve Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, OX40,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Tumor Necrosis Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Tnfrsf18 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Tnfrsf4 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Tnfrsf4 protein, rat
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
|
pubmed:issn |
0006-4971
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pubmed:author |
|
pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
105
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pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
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pubmed:pagination |
2845-51
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:15591118-Animals,
pubmed-meshheading:15591118-Antibodies, Monoclonal,
pubmed-meshheading:15591118-Bone Marrow Transplantation,
pubmed-meshheading:15591118-CD4-Positive T-Lymphocytes,
pubmed-meshheading:15591118-Cell Division,
pubmed-meshheading:15591118-Glucocorticoid-Induced TNFR-Related Protein,
pubmed-meshheading:15591118-Graft vs Host Disease,
pubmed-meshheading:15591118-Interleukin-2,
pubmed-meshheading:15591118-Lymphocyte Activation,
pubmed-meshheading:15591118-Mice,
pubmed-meshheading:15591118-Mice, Inbred BALB C,
pubmed-meshheading:15591118-Mice, Inbred C57BL,
pubmed-meshheading:15591118-Mice, Mutant Strains,
pubmed-meshheading:15591118-Rats,
pubmed-meshheading:15591118-Rats, Wistar,
pubmed-meshheading:15591118-Receptors, Interleukin-2,
pubmed-meshheading:15591118-Receptors, Nerve Growth Factor,
pubmed-meshheading:15591118-Receptors, OX40,
pubmed-meshheading:15591118-Receptors, Tumor Necrosis Factor
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pubmed:year |
2005
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pubmed:articleTitle |
Triggering of OX40 (CD134) on CD4(+)CD25+ T cells blocks their inhibitory activity: a novel regulatory role for OX40 and its comparison with GITR.
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pubmed:affiliation |
Immunotherapy and Gene Therapy Unit, Department of Experimental Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori, Via Venezian 1, 20133 Milan, Italy.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
|