rdf:type |
|
lifeskim:mentions |
|
pubmed:issue |
4
|
pubmed:dateCreated |
2008-4-3
|
pubmed:abstractText |
Engagement of glucocorticoid-induced TNFR-related protein (GITR) enables the costimulation of both CD25(-)CD4(+) effector (Teff) and CD25(+)CD4(+) regulatory (Treg) cells; however, the effects of GITR-costimulation on Treg function remain controversial. In this study, we examined the effects of GITR ligand (GITRL) binding on the respective functions of CD4(+) T cells. GITRL-P815 transfectants efficiently augmented anti-CD3-induced proliferation and cytokine production by Teff cells. Proliferation and IL-10 production in Treg were also enhanced by GITRL transfectants when exogenous IL-2 and stronger CD3 stimulation was provided. Concomitant GITRL-costimulation of Teff and Treg converted the anergic state of Treg into a proliferating state, maintaining and augmenting their function. Thus, GITRL-costimulation augments both effector and regulatory functions of CD4(+) T cells. Our results suggest that highly activated and increased ratios of Treg reverse the immune-enhancing effects of GITRL-costimulation in Teff, which may be problematic for therapeutic applications using strong GITR agonists.
|
pubmed:language |
eng
|
pubmed:journal |
|
pubmed:citationSubset |
IM
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Monoclonal,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD3,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD4,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-10,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-2 Receptor alpha Subunit,
http://linkedlifedata.com/resource/pubmed/chemical/Ligands,
http://linkedlifedata.com/resource/pubmed/chemical/Tnfsf18 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factors
|
pubmed:status |
MEDLINE
|
pubmed:month |
May
|
pubmed:issn |
1090-2104
|
pubmed:author |
|
pubmed:issnType |
Electronic
|
pubmed:day |
16
|
pubmed:volume |
369
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
1134-8
|
pubmed:meshHeading |
pubmed-meshheading:18346459-Animals,
pubmed-meshheading:18346459-Antibodies, Monoclonal,
pubmed-meshheading:18346459-Antigen-Presenting Cells,
pubmed-meshheading:18346459-Antigens, CD3,
pubmed-meshheading:18346459-Antigens, CD4,
pubmed-meshheading:18346459-Coculture Techniques,
pubmed-meshheading:18346459-Female,
pubmed-meshheading:18346459-Interleukin-10,
pubmed-meshheading:18346459-Interleukin-2 Receptor alpha Subunit,
pubmed-meshheading:18346459-Ligands,
pubmed-meshheading:18346459-Lymphocyte Activation,
pubmed-meshheading:18346459-Mice,
pubmed-meshheading:18346459-Mice, Inbred BALB C,
pubmed-meshheading:18346459-T-Lymphocytes, Regulatory,
pubmed-meshheading:18346459-Transfection,
pubmed-meshheading:18346459-Tumor Necrosis Factors
|
pubmed:year |
2008
|
pubmed:articleTitle |
GITR ligand-costimulation activates effector and regulatory functions of CD4+ T cells.
|
pubmed:affiliation |
Department of Molecular Immunology, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, Japan.
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|