Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2007-9-20
pubmed:abstractText
OX40 is a recently identified T-cell costimulatory molecule that belongs to the TNF/TNFR superfamily. OX40 can be expressed by both activated T effector cells and Foxp3(+) Tregs. It is well known that OX40 delivers a potent costimulatory signal to T effector cells, but very little is known about the role of OX40 in regulating the suppressor properties of Foxp3(+) Tregs and the de novo generation of new inducible Foxp3(+) Tregs from T effector cells. In the present study, we found, by using a newly created foxp3gfp knockin model, that OX40 was dispensable for the genesis and suppressor functions of naturally arising CD4(+)Foxp3(+) Tregs, but stimulating OX40 on the Foxp3(+) Tregs abrogated their ability to suppress T effector cell proliferation, IFN-gamma production, and T effector cell-mediated allograft rejection. OX40 costimulation did not significantly affect proliferation and survival of the naturally arising Foxp3(+) Tregs, but profoundly inhibited Foxp3 gene expression. Importantly, OX40 costimulation to T effector cells prevented the induction of new inducible Foxp3(+) Tregs from T effector cells. Our study identified OX40 as a key negative regulator of Foxp3(+) Tregs and may have important clinical implications in models of transplantation and autoimmunity.
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/17575071-10202046, http://linkedlifedata.com/resource/pubmed/commentcorrection/17575071-10586044, http://linkedlifedata.com/resource/pubmed/commentcorrection/17575071-10626891, http://linkedlifedata.com/resource/pubmed/commentcorrection/17575071-10637265, http://linkedlifedata.com/resource/pubmed/commentcorrection/17575071-10733518, http://linkedlifedata.com/resource/pubmed/commentcorrection/17575071-10795741, http://linkedlifedata.com/resource/pubmed/commentcorrection/17575071-10888927, http://linkedlifedata.com/resource/pubmed/commentcorrection/17575071-11035773, http://linkedlifedata.com/resource/pubmed/commentcorrection/17575071-11135625, http://linkedlifedata.com/resource/pubmed/commentcorrection/17575071-11157058, http://linkedlifedata.com/resource/pubmed/commentcorrection/17575071-11238558, http://linkedlifedata.com/resource/pubmed/commentcorrection/17575071-11479622, http://linkedlifedata.com/resource/pubmed/commentcorrection/17575071-11509650, http://linkedlifedata.com/resource/pubmed/commentcorrection/17575071-11812990, http://linkedlifedata.com/resource/pubmed/commentcorrection/17575071-12521997, http://linkedlifedata.com/resource/pubmed/commentcorrection/17575071-12522256, http://linkedlifedata.com/resource/pubmed/commentcorrection/17575071-12612578, http://linkedlifedata.com/resource/pubmed/commentcorrection/17575071-12626546, http://linkedlifedata.com/resource/pubmed/commentcorrection/17575071-12658268, http://linkedlifedata.com/resource/pubmed/commentcorrection/17575071-12860930, http://linkedlifedata.com/resource/pubmed/commentcorrection/17575071-12974476, http://linkedlifedata.com/resource/pubmed/commentcorrection/17575071-14500627, http://linkedlifedata.com/resource/pubmed/commentcorrection/17575071-14634111, http://linkedlifedata.com/resource/pubmed/commentcorrection/17575071-14676299, http://linkedlifedata.com/resource/pubmed/commentcorrection/17575071-14734751, http://linkedlifedata.com/resource/pubmed/commentcorrection/17575071-15004159, http://linkedlifedata.com/resource/pubmed/commentcorrection/17575071-15032588, http://linkedlifedata.com/resource/pubmed/commentcorrection/17575071-15173831, http://linkedlifedata.com/resource/pubmed/commentcorrection/17575071-15218097, http://linkedlifedata.com/resource/pubmed/commentcorrection/17575071-15470044, http://linkedlifedata.com/resource/pubmed/commentcorrection/17575071-15528328, http://linkedlifedata.com/resource/pubmed/commentcorrection/17575071-15585848, http://linkedlifedata.com/resource/pubmed/commentcorrection/17575071-15591118, http://linkedlifedata.com/resource/pubmed/commentcorrection/17575071-15630140, http://linkedlifedata.com/resource/pubmed/commentcorrection/17575071-15753210, http://linkedlifedata.com/resource/pubmed/commentcorrection/17575071-15785757, http://linkedlifedata.com/resource/pubmed/commentcorrection/17575071-16147528, http://linkedlifedata.com/resource/pubmed/commentcorrection/17575071-16244650, http://linkedlifedata.com/resource/pubmed/commentcorrection/17575071-16393983, http://linkedlifedata.com/resource/pubmed/commentcorrection/17575071-16424166, http://linkedlifedata.com/resource/pubmed/commentcorrection/17575071-16424940, http://linkedlifedata.com/resource/pubmed/commentcorrection/17575071-16557261, http://linkedlifedata.com/resource/pubmed/commentcorrection/17575071-16648838, http://linkedlifedata.com/resource/pubmed/commentcorrection/17575071-16924108, http://linkedlifedata.com/resource/pubmed/commentcorrection/17575071-7481803, http://linkedlifedata.com/resource/pubmed/commentcorrection/17575071-8228223, http://linkedlifedata.com/resource/pubmed/commentcorrection/17575071-9036940
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
110
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2501-10
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
OX40 costimulation turns off Foxp3+ Tregs.
pubmed:affiliation
Harvard Medical School, Transplant Research Center, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural