title: T cell intrinsic roles of autophagy in promoting adaptive immunity.
abstract: Autophagy, an ancient cellular response where autophagic vacuoles are formed within the cytosol, is induced in response to a variety of cellular insults, including growth factor or nutrient withdrawal, organelle damage, and misfolded proteins. Autophagy is rapidly induced in T lymphocytes following antigenic stimulation and blockade of autophagic signaling greatly reduces T cell clonal expansion, suggesting that autophagy is primarily involved in promoting T cell survival. In contrast, a recently identified negative feedback loop involving FADD and caspase-8 limits the level of autophagy in T cells. Failure to activate caspase-8 during T cell mitogenesis leads to hyperactive autophagy and cellular death through a programmed necrotic mechanism. These findings suggest that crosstalk between these cellular processes is essential for T cell activation and homeostasis.
authors.affiliation: The Institute for Immunology, University of California, Irvine, CA 92697-3900, USA. cwalsh@uci.edu
authors.forename: Craig M
authors.initials: CM
authors.lastname: Walsh
authors.forename: Bryan D
authors.initials: BD
authors.lastname: Bell
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology*; D000818:Animals; D017209:Apoptosis; D001343:Autophagy / Q000276:immunology*; D053181:Caspase 8 / Q000378:metabolism; D053200:Fas-Associated Death Domain Protein / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology
chemical_list: D053200:Fas-Associated Death Domain Protein; D053181:Caspase 8
references.citation: J Immunol. 2009 Apr 1;182(7):4046-55
references.pmid: 19299702
references.citation: Curr Neuropharmacol. 2008 Jun;6(2):97-101
references.pmid: 19305790
references.citation: J Biol Chem. 2000 Sep 22;275(38):29900-6
references.pmid: 10893413
references.citation: Cell. 2008 Dec 26;135(7):1311-23
references.pmid: 19109899
references.citation: J Clin Invest. 2006 Aug;116(8):2161-72
references.pmid: 16886061
references.citation: J Immunol. 2003 Jul 1;171(1):247-56
references.pmid: 12817005
references.citation: J Clin Invest. 2009 May;119(5):1359-72
references.pmid: 19425170
references.citation: EMBO J. 2000 Nov 1;19(21):5720-8
references.pmid: 11060023
references.citation: J Cell Sci. 2004 Jun 1;117(Pt 13):2805-12
references.pmid: 15169837
references.citation: Nature. 2002 Sep 26;419(6905):395-9
references.pmid: 12353035
references.citation: J Biol Chem. 2005 May 27;280(21):20722-9
references.pmid: 15778222
references.citation: Immunity. 1998 Apr;8(4):439-49
references.pmid: 9586634
references.citation: Nat Cell Biol. 2004 Dec;6(12):1221-8
references.pmid: 15558033
references.citation: Proc Natl Acad Sci U S A. 2008 Oct 28;105(43):16677-82
references.pmid: 18946037
references.citation: J Immunol. 2006 Oct 15;177(8):5163-8
references.pmid: 17015701
references.citation: Science. 2004 Jun 4;304(5676):1500-2
references.pmid: 15131264
references.citation: J Cell Biol. 2000 Sep 18;150(6):1507-13
references.pmid: 10995454
references.citation: EMBO J. 1998 Feb 2;17(3):706-18
references.pmid: 9450996
references.citation: J Exp Med. 1999 Dec 20;190(12):1891-6
references.pmid: 10601363
references.citation: Autophagy. 2009 Jul;5(5):720-2
references.pmid: 19395874
references.citation: Cell. 2007 Dec 14;131(6):1137-48
references.pmid: 18083103
references.citation: Autophagy. 2009 Jul;5(5):590-603
references.pmid: 19363298
references.citation: J Exp Med. 2007 Jan 22;204(1):25-31
references.pmid: 17190837
references.citation: Curr Opin Cell Biol. 2004 Dec;16(6):663-9
references.pmid: 15530778
references.citation: Cell Death Differ. 2009 Jul;16(7):939-46
references.pmid: 19229244
references.citation: Cell Death Differ. 2009 Jul;16(7):933-4
references.pmid: 19528948
references.citation: J Cell Biol. 2001 Feb 5;152(3):519-30
references.pmid: 11157979
references.citation: Curr Biol. 1998 Apr 9;8(8):467-70
references.pmid: 9550704
references.citation: J Clin Immunol. 2003 Sep;23(5):333-53
references.pmid: 14601642
references.citation: J Biol Chem. 1998 Feb 13;273(7):3963-6
references.pmid: 9461583
references.citation: J Exp Med. 1999 Dec 20;190(12):1879-90
references.pmid: 10601362
references.citation: Science. 2002 Apr 12;296(5566):301-5
references.pmid: 11951032
references.citation: Cell. 2009 Jun 12;137(6):1100-11
references.pmid: 19524512
references.citation: Nat Immunol. 2000 Dec;1(6):489-95
references.pmid: 11101870
references.citation: Autophagy. 2008 Feb;4(2):151-75
references.pmid: 18188003
references.citation: Nature. 2007 Dec 20;450(7173):1253-7
references.pmid: 18097414
references.citation: J Biol Chem. 2006 Dec 1;281(48):36883-90
references.pmid: 17005556
references.citation: Autophagy. 2009 Feb;5(2):238-40
references.pmid: 19077534
references.citation: Genes Dev. 2003 Apr 1;17(7):883-95
references.pmid: 12654726
references.citation: Immunity. 2009 Apr 17;30(4):479-81
references.pmid: 19371713
references.citation: Autophagy. 2009 Jul;5(5):625-35
references.pmid: 19276668
references.citation: Immunity. 2002 Jun;16(6):769-77
references.pmid: 12121659
references.citation: Proc Natl Acad Sci U S A. 2008 Nov 11;105(45):17463-8
references.pmid: 18981423
references.citation: Cell. 2009 Jun 12;137(6):1112-23
references.pmid: 19524513
references.citation: Nat Chem Biol. 2005 Jul;1(2):112-9
references.pmid: 16408008
references.citation: Mol Cell. 2009 May 15;34(3):259-69
references.pmid: 19450525
references.citation: Science. 2009 Jul 17;325(5938):332-6
references.pmid: 19498109
references.citation: Nat Immunol. 2001 May;2(5):423-9
references.pmid: 11323696
references.citation: Mol Biol Cell. 2009 Apr;20(7):1992-2003
references.pmid: 19225151
references.citation: Autophagy. 2009 May;5(4):569-70
references.pmid: 19398886
references.citation: Autophagy. 2008 Apr;4(3):309-14
references.pmid: 18188005
references.citation: Curr Biol. 2001 Feb 20;11(4):273-6
references.pmid: 11250157
references.citation: J Cell Biol. 2001 Feb 19;152(4):657-68
references.pmid: 11266458
references.citation: Autophagy. 2005 Jul;1(2):84-91
references.pmid: 16874052
references.citation: J Immunol. 2007 Oct 15;179(8):5291-300
references.pmid: 17911615
references.citation: Int J Biochem Cell Biol. 2004 Dec;36(12):2503-18
references.pmid: 15325588
references.citation: Nat Chem Biol. 2008 May;4(5):313-21
references.pmid: 18408713
references.citation: Nature. 1998 Mar 19;392(6673):296-300
references.pmid: 9521326
references.citation: Curr Top Microbiol Immunol. 2009;335:71-84
references.pmid: 19802560
references.citation: Cell Death Differ. 2009 Jul;16(7):966-75
references.pmid: 19325568