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- Publisher Website: 10.1073/pnas.0911573106
- Scopus: eid_2-s2.0-73949090666
- PMID: 19915142
- WOS: WOS:000272254400044
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Article: Inducible costimulator promotes helper T-cell differentiation through phosphoinositide 3-kinase
Title | Inducible costimulator promotes helper T-cell differentiation through phosphoinositide 3-kinase |
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Authors | |
Keywords | CD28 Follicular B helper T-cell ICOS PI3K Germinal center |
Issue Date | 2009 |
Citation | Proceedings of the National Academy of Sciences of the United States of America, 2009, v. 106, n. 48, p. 20371-20376 How to Cite? |
Abstract | The T-cell costimulatory receptors, CD28 and the inducible costimulator (ICOS), are required for the generation of follicular B helper T cells (TFH) and germinal center (GC) reaction. A common signal transducer used by CD28 and ICOS is the phosphoinositide 3-kinase (PI3K). Although it is known that CD28-mediated PI3K activation is dispensable for GC reaction, the role of ICOS-driven PI3K signaling has not been defined. We show here that knock-in mice that selectively lost the ability to activate PI3K through ICOS had severe defects in TFH generation, GC reaction, antibody class switch, and antibody affinity maturation. In preactivated CD4+ T cells, ICOS delivered a potent PI3K signal that was critical for the induction of the key TFH cytokines, IL-21 and IL-4. Under the same settings, CD28 was unable to activate PI3K but supported a robust secondary expansion of T cells. Thus, our results demonstrate a nonredundant function of ICOS-PI3K pathway in the generation of TFH and suggest that CD28 and ICOS play differential roles during a multistep process of TFH differentiation. |
Persistent Identifier | http://hdl.handle.net/10722/291936 |
ISSN | 2023 Impact Factor: 9.4 2023 SCImago Journal Rankings: 3.737 |
PubMed Central ID | |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Gigoux, Mathieu | - |
dc.contributor.author | Shang, Jijun | - |
dc.contributor.author | Pak, Youngshil | - |
dc.contributor.author | Xu, Minghong | - |
dc.contributor.author | Choe, Jongseon | - |
dc.contributor.author | Mak, Tak W. | - |
dc.contributor.author | Suh, Woong Kyung | - |
dc.date.accessioned | 2020-11-17T14:55:25Z | - |
dc.date.available | 2020-11-17T14:55:25Z | - |
dc.date.issued | 2009 | - |
dc.identifier.citation | Proceedings of the National Academy of Sciences of the United States of America, 2009, v. 106, n. 48, p. 20371-20376 | - |
dc.identifier.issn | 0027-8424 | - |
dc.identifier.uri | http://hdl.handle.net/10722/291936 | - |
dc.description.abstract | The T-cell costimulatory receptors, CD28 and the inducible costimulator (ICOS), are required for the generation of follicular B helper T cells (TFH) and germinal center (GC) reaction. A common signal transducer used by CD28 and ICOS is the phosphoinositide 3-kinase (PI3K). Although it is known that CD28-mediated PI3K activation is dispensable for GC reaction, the role of ICOS-driven PI3K signaling has not been defined. We show here that knock-in mice that selectively lost the ability to activate PI3K through ICOS had severe defects in TFH generation, GC reaction, antibody class switch, and antibody affinity maturation. In preactivated CD4+ T cells, ICOS delivered a potent PI3K signal that was critical for the induction of the key TFH cytokines, IL-21 and IL-4. Under the same settings, CD28 was unable to activate PI3K but supported a robust secondary expansion of T cells. Thus, our results demonstrate a nonredundant function of ICOS-PI3K pathway in the generation of TFH and suggest that CD28 and ICOS play differential roles during a multistep process of TFH differentiation. | - |
dc.language | eng | - |
dc.relation.ispartof | Proceedings of the National Academy of Sciences of the United States of America | - |
dc.subject | CD28 | - |
dc.subject | Follicular B helper T-cell | - |
dc.subject | ICOS | - |
dc.subject | PI3K | - |
dc.subject | Germinal center | - |
dc.title | Inducible costimulator promotes helper T-cell differentiation through phosphoinositide 3-kinase | - |
dc.type | Article | - |
dc.description.nature | link_to_OA_fulltext | - |
dc.identifier.doi | 10.1073/pnas.0911573106 | - |
dc.identifier.pmid | 19915142 | - |
dc.identifier.pmcid | PMC2787139 | - |
dc.identifier.scopus | eid_2-s2.0-73949090666 | - |
dc.identifier.volume | 106 | - |
dc.identifier.issue | 48 | - |
dc.identifier.spage | 20371 | - |
dc.identifier.epage | 20376 | - |
dc.identifier.eissn | 1091-6490 | - |
dc.identifier.isi | WOS:000272254400044 | - |
dc.identifier.issnl | 0027-8424 | - |