Inducible costimulator promotes helper T-cell differentiation through phosphoinositide 3-kinase

The T-cell costimulatory receptors, CD28 and the inducible costimulator (ICOS), are required for the generation of follicular B helper T cells (T(FH)) and germinal center (GC) reaction. A common signal transducer used by CD28 and ICOS is the phosphoinositide 3-kinase (PI3K). Although it is known tha...

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Veröffentlicht in:	Proceedings of the National Academy of Sciences - PNAS Jg. 106; H. 48; S. 20371
Hauptverfasser:	Gigoux, Mathieu, Shang, Jijun, Pak, Youngshil, Xu, Minghong, Choe, Jongseon, Mak, Tak W, Suh, Woong-Kyung
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	United States 01.12.2009
Schlagworte:	Animals Antigens, Differentiation, T-Lymphocyte - immunology Antigens, Differentiation, T-Lymphocyte - metabolism CD28 Antigens - immunology CD28 Antigens - metabolism CD4-Positive T-Lymphocytes - metabolism Cell Differentiation - immunology Enzyme-Linked Immunosorbent Assay Immunoprecipitation Inducible T-Cell Co-Stimulator Protein Interleukin-4 - immunology Interleukins - immunology Mice Mice, Transgenic Phosphatidylinositol 3-Kinases - immunology Phosphatidylinositol 3-Kinases - metabolism Signal Transduction - immunology T-Lymphocytes, Helper-Inducer - immunology
ISSN:	1091-6490, 1091-6490
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Abstract	The T-cell costimulatory receptors, CD28 and the inducible costimulator (ICOS), are required for the generation of follicular B helper T cells (T(FH)) 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 T(FH) 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 T(FH) 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 T(FH) and suggest that CD28 and ICOS play differential roles during a multistep process of T(FH) differentiation.
AbstractList	The T-cell costimulatory receptors, CD28 and the inducible costimulator (ICOS), are required for the generation of follicular B helper T cells (T(FH)) 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 T(FH) 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 T(FH) 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 T(FH) and suggest that CD28 and ICOS play differential roles during a multistep process of T(FH) differentiation.The T-cell costimulatory receptors, CD28 and the inducible costimulator (ICOS), are required for the generation of follicular B helper T cells (T(FH)) 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 T(FH) 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 T(FH) 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 T(FH) and suggest that CD28 and ICOS play differential roles during a multistep process of T(FH) differentiation. The T-cell costimulatory receptors, CD28 and the inducible costimulator (ICOS), are required for the generation of follicular B helper T cells (T(FH)) 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 T(FH) 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 T(FH) 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 T(FH) and suggest that CD28 and ICOS play differential roles during a multistep process of T(FH) differentiation.
Author	Suh, Woong-Kyung Gigoux, Mathieu Mak, Tak W Xu, Minghong Choe, Jongseon Shang, Jijun Pak, Youngshil
Author_xml	– sequence: 1 givenname: Mathieu surname: Gigoux fullname: Gigoux, Mathieu organization: Institut de recherches cliniques de Montréal, Montréal, Canada H2W 1R7 – sequence: 2 givenname: Jijun surname: Shang fullname: Shang, Jijun – sequence: 3 givenname: Youngshil surname: Pak fullname: Pak, Youngshil – sequence: 4 givenname: Minghong surname: Xu fullname: Xu, Minghong – sequence: 5 givenname: Jongseon surname: Choe fullname: Choe, Jongseon – sequence: 6 givenname: Tak W surname: Mak fullname: Mak, Tak W – sequence: 7 givenname: Woong-Kyung surname: Suh fullname: Suh, Woong-Kyung
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/19915142$$D View this record in MEDLINE/PubMed
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References	19221396 - J Exp Med. 2009 Mar 16;206(3):561-76 19252490 - Nat Immunol. 2009 Apr;10(4):385-93 16982935 - J Immunol. 2006 Oct 1;177(7):4927-32 19299705 - J Immunol. 2009 Apr 1;182(7):4076-84 12853164 - Immunol Lett. 2003 Jul 3;88(1):63-70 16081804 - J Immunol. 2005 Aug 15;175(4):2340-8 12577056 - Nat Immunol. 2003 Mar;4(3):261-8 11343122 - Nature. 2001 Jan 4;409(6816):102-5 11910893 - Nat Rev Immunol. 2002 Feb;2(2):116-26 18599325 - Immunity. 2008 Jul 18;29(1):138-49 17336157 - Trends Immunol. 2007 Apr;28(4):161-8 19608860 - Science. 2009 Aug 21;325(5943):1006-10 19217324 - Immunity. 2009 Feb 20;30(2):228-41 19631565 - Immunity. 2009 Sep 18;31(3):457-68 17603562 - Oncogene. 2007 Dec 6;26(55):7709-14 9930702 - Nature. 1999 Jan 21;397(6716):263-6 10523609 - J Exp Med. 1999 Oct 18;190(8):1115-22 15917799 - Nature. 2005 May 26;435(7041):452-8 19144318 - Immunity. 2009 Jan 16;30(1):120-9 18641334 - J Immunol. 2008 Aug 1;181(3):1969-77 19155489 - J Immunol. 2009 Feb 1;182(3):1421-8 12496387 - J Immunol. 2003 Jan 1;170(1):91-8 18056361 - J Immunol. 2007 Dec 15;179(12):8180-90 12130661 - Science. 2002 Aug 9;297(5583):1031-4 15771580 - Annu Rev Immunol. 2005;23:515-48 8921969 - Eur J Immunol. 1996 Nov;26(11):2781-9 11343123 - Nature. 2001 Jan 4;409(6816):105-9 17617602 - J Immunol. 2007 Jul 15;179(2):1096-103 18602282 - Immunity. 2008 Jul 18;29(1):127-37 19095735 - J Leukoc Biol. 2009 Mar;85(3):526-38 12039907 - Int Immunol. 2002 Jun;14(6):555-66 18172933 - Nature. 2007 Nov 8;450(7167):299-303 19398586 - Mol Cell Biol. 2009 Jul;29(13):3710-21 19139170 - J Exp Med. 2009 Jan 16;206(1):69-78 9651253 - Science. 1998 Jul 3;281(5373):96-9 11343121 - Nature. 2001 Jan 4;409(6816):97-101 18483500 - Nat Rev Immunol. 2008 Jun;8(6):421-34 10508261 - Eur J Immunol. 1999 Sep;29(9):2863-74 12594849 - Eur J Immunol. 2003 Jan;33(1):204-14 8648099 - J Immunol. 1996 Jun 15;156(12):4576-81 19628815 - Science. 2009 Aug 21;325(5943):1001-5 16261173 - Nat Rev Immunol. 2005 Nov;5(11):853-65 12538658 - J Exp Med. 2003 Jan 20;197(2):181-93 12594252 - J Immunol. 2003 Mar 1;170(5):2310-5 12816995 - J Immunol. 2003 Jul 1;171(1):166-74 9469426 - J Immunol. 1998 Feb 15;160(4):1694-700 11046032 - J Immunol. 2000 Nov 1;165(9):5035-40
References_xml	– reference: 15917799 - Nature. 2005 May 26;435(7041):452-8 – reference: 16261173 - Nat Rev Immunol. 2005 Nov;5(11):853-65 – reference: 11343121 - Nature. 2001 Jan 4;409(6816):97-101 – reference: 9930702 - Nature. 1999 Jan 21;397(6716):263-6 – reference: 12039907 - Int Immunol. 2002 Jun;14(6):555-66 – reference: 17617602 - J Immunol. 2007 Jul 15;179(2):1096-103 – reference: 8648099 - J Immunol. 1996 Jun 15;156(12):4576-81 – reference: 15771580 - Annu Rev Immunol. 2005;23:515-48 – reference: 9651253 - Science. 1998 Jul 3;281(5373):96-9 – reference: 19155489 - J Immunol. 2009 Feb 1;182(3):1421-8 – reference: 19139170 - J Exp Med. 2009 Jan 16;206(1):69-78 – reference: 10508261 - Eur J Immunol. 1999 Sep;29(9):2863-74 – reference: 12130661 - Science. 2002 Aug 9;297(5583):1031-4 – reference: 18641334 - J Immunol. 2008 Aug 1;181(3):1969-77 – reference: 10523609 - J Exp Med. 1999 Oct 18;190(8):1115-22 – reference: 8921969 - Eur J Immunol. 1996 Nov;26(11):2781-9 – reference: 17336157 - Trends Immunol. 2007 Apr;28(4):161-8 – reference: 19398586 - Mol Cell Biol. 2009 Jul;29(13):3710-21 – reference: 19252490 - Nat Immunol. 2009 Apr;10(4):385-93 – reference: 19217324 - Immunity. 2009 Feb 20;30(2):228-41 – reference: 12538658 - J Exp Med. 2003 Jan 20;197(2):181-93 – reference: 18599325 - Immunity. 2008 Jul 18;29(1):138-49 – reference: 16081804 - J Immunol. 2005 Aug 15;175(4):2340-8 – reference: 9469426 - J Immunol. 1998 Feb 15;160(4):1694-700 – reference: 11046032 - J Immunol. 2000 Nov 1;165(9):5035-40 – reference: 18483500 - Nat Rev Immunol. 2008 Jun;8(6):421-34 – reference: 12496387 - J Immunol. 2003 Jan 1;170(1):91-8 – reference: 11343123 - Nature. 2001 Jan 4;409(6816):105-9 – reference: 16982935 - J Immunol. 2006 Oct 1;177(7):4927-32 – reference: 11910893 - Nat Rev Immunol. 2002 Feb;2(2):116-26 – reference: 12594849 - Eur J Immunol. 2003 Jan;33(1):204-14 – reference: 12816995 - J Immunol. 2003 Jul 1;171(1):166-74 – reference: 18056361 - J Immunol. 2007 Dec 15;179(12):8180-90 – reference: 11343122 - Nature. 2001 Jan 4;409(6816):102-5 – reference: 19631565 - Immunity. 2009 Sep 18;31(3):457-68 – reference: 18602282 - Immunity. 2008 Jul 18;29(1):127-37 – reference: 19144318 - Immunity. 2009 Jan 16;30(1):120-9 – reference: 19221396 - J Exp Med. 2009 Mar 16;206(3):561-76 – reference: 19628815 - Science. 2009 Aug 21;325(5943):1001-5 – reference: 19299705 - J Immunol. 2009 Apr 1;182(7):4076-84 – reference: 12577056 - Nat Immunol. 2003 Mar;4(3):261-8 – reference: 12853164 - Immunol Lett. 2003 Jul 3;88(1):63-70 – reference: 18172933 - Nature. 2007 Nov 8;450(7167):299-303 – reference: 19095735 - J Leukoc Biol. 2009 Mar;85(3):526-38 – reference: 17603562 - Oncogene. 2007 Dec 6;26(55):7709-14 – reference: 19608860 - Science. 2009 Aug 21;325(5943):1006-10 – reference: 12594252 - J Immunol. 2003 Mar 1;170(5):2310-5
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Snippet	The T-cell costimulatory receptors, CD28 and the inducible costimulator (ICOS), are required for the generation of follicular B helper T cells (T(FH)) and...
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SubjectTerms	Animals Antigens, Differentiation, T-Lymphocyte - immunology Antigens, Differentiation, T-Lymphocyte - metabolism CD28 Antigens - immunology CD28 Antigens - metabolism CD4-Positive T-Lymphocytes - metabolism Cell Differentiation - immunology Enzyme-Linked Immunosorbent Assay Immunoprecipitation Inducible T-Cell Co-Stimulator Protein Interleukin-4 - immunology Interleukins - immunology Mice Mice, Transgenic Phosphatidylinositol 3-Kinases - immunology Phosphatidylinositol 3-Kinases - metabolism Signal Transduction - immunology T-Lymphocytes, Helper-Inducer - immunology
Title	Inducible costimulator promotes helper T-cell differentiation through phosphoinositide 3-kinase
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