title: CD8 T cells utilize TRAIL to control influenza virus infection.
abstract: Elimination of influenza virus-infected cells during primary influenza virus infections is thought to be mediated by CD8(+) T cells though perforin- and FasL-mediated mechanisms. However, recent studies suggest that CD8(+) T cells can also utilize TRAIL to kill virally infected cells. Therefore, we herein examined the importance of TRAIL to influenza-specific CD8(+) T cell immunity and to the control of influenza virus infections. Our results show that TRAIL deficiency increases influenza-associated morbidity and influenza virus titers, and that these changes in disease severity are coupled to decreased influenza-specific CD8(+) T cell cytotoxicity in TRAIL(-/-) mice, a decrease that occurs despite equivalent numbers of pulmonary influenza-specific CD8(+) T cells. Furthermore, TRAIL expression occurs selectively on influenza-specific CD8(+) T cells, and high TRAIL receptor (DR5) expression occurs selectively on influenza virus-infected pulmonary epithelial cells. Finally, we show that adoptive transfer of TRAIL(+/+) but not TRAIL(-/-) CD8(+) effector T cells alters the mortality associated with lethal dose influenza virus infections. Collectively, our results suggest that TRAIL is an important component of immunity to influenza infections and that TRAIL deficiency decreases CD8(+) T cell-mediated cytotoxicity, leading to more severe influenza infections.
authors.affiliation: Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Erik L
authors.initials: EL
authors.lastname: Brincks
authors.forename: Arna
authors.initials: A
authors.lastname: Katewa
authors.forename: Tamara A
authors.initials: TA
authors.lastname: Kucaba
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Griffith
authors.forename: Kevin L
authors.initials: KL
authors.lastname: Legge
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000821:virology*; D002460:Cell Line; D053118:Influenza A Virus, H1N1 Subtype / Q000254:growth & development / Q000276:immunology*; D008168:Lung / Q000276:immunology / Q000473:pathology / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009976:Orthomyxoviridae Infections / Q000401:mortality / Q000473:pathology / Q000517:prevention & control* / Q000821:virology; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D019562:Viral Load; D015431:Weight Loss / Q000235:genetics / Q000276:immunology
chemical_list: D053221:TNF-Related Apoptosis-Inducing Ligand; C505654:Tnfsf10 protein, mouse
references.citation: J Immunol. 2000 Dec 15;165(12):6833-9
references.pmid: 11120806
references.citation: J Exp Med. 2007 Mar 19;204(3):667-80
references.pmid: 17353365
references.citation: Nat Immunol. 2001 May;2(5):381-2
references.pmid: 11323687
references.citation: J Virol. 2001 Nov;75(22):11128-36
references.pmid: 11602752
references.citation: Eur J Immunol. 2001 Nov;31(11):3138-46
references.pmid: 11745330
references.citation: Gastroenterology. 2002 Mar;122(3):659-66
references.pmid: 11874999
references.citation: Eur J Immunol. 2002 Aug;32(8):2246-54
references.pmid: 12209637
references.citation: Immunity. 2003 Feb;18(2):265-77
references.pmid: 12594953
references.citation: Nat Immunol. 2003 Apr;4(4):361-5
references.pmid: 12640451
references.citation: J Immunol. 2003 Jul 1;171(1):212-8
references.pmid: 12817000
references.citation: J Virol. 2003 Sep;77(17):9156-72
references.pmid: 12915532
references.citation: Genes Cells. 2004 Feb;9(2):165-74
references.pmid: 15009093
references.citation: J Immunol. 2004 Jul 15;173(2):1209-18
references.pmid: 15240712
references.citation: Viral Immunol. 2004;17(2):197-209
references.pmid: 15279699
references.citation: Blood. 2004 Oct 15;104(8):2418-24
references.pmid: 15205263
references.citation: J Exp Med. 1984 Sep 1;160(3):814-26
references.pmid: 6206190
references.citation: Am J Respir Crit Care Med. 1995 Oct;152(4 Pt 2):S67-71
references.pmid: 7551417
references.citation: Curr Top Microbiol Immunol. 1996;206:1-14
references.pmid: 8608712
references.citation: J Biol Chem. 1996 May 31;271(22):12687-90
references.pmid: 8663110
references.citation: J Immunol. 1996 Dec 15;157(12):5555-62
references.pmid: 8955206
references.citation: J Virol. 1998 Jan;72(1):882-5
references.pmid: 9420305
references.citation: J Immunol. 1997 Dec 1;159(11):5197-200
references.pmid: 9548456
references.citation: J Immunol. 1998 Jan 1;160(1):322-7
references.pmid: 9551987
references.citation: Eur J Immunol. 1998 May;28(5):1492-8
references.pmid: 9603453
references.citation: J Exp Med. 1999 Apr 19;189(8):1343-54
references.pmid: 10209050
references.citation: J Immunol. 1999 Jul 15;163(2):920-6
references.pmid: 10395688
references.citation: J Immunol. 2005 Jan 15;174(2):696-701
references.pmid: 15634888
references.citation: Mol Cell Biol. 2005 Mar;25(5):2000-13
references.pmid: 15713653
references.citation: J Immunol. 2005 May 1;174(9):5332-40
references.pmid: 15843530
references.citation: J Virol. 2000 Jan;74(1):556-9
references.pmid: 10590149
references.citation: J Virol. 2000 Apr;74(8):3486-93
references.pmid: 10729122
references.citation: J Immunol. 2007 Jul 1;179(1):64-70
references.pmid: 17579022
references.citation: J Virol. 2007 Sep;81(18):9790-800
references.pmid: 17626092
references.citation: J Immunol. 2008 Jan 1;180(1):25-9
references.pmid: 18096998
references.citation: J Virol. 2000 Jul;74(13):6105-16
references.pmid: 10846094
references.citation: Am J Pathol. 2001 Jan;158(1):119-30
references.pmid: 11141485
references.citation: J Virol. 2005 Jun;79(12):7658-63
references.pmid: 15919918
references.citation: J Leukoc Biol. 2005 Aug;78(2):359-71
references.pmid: 15937142
references.citation: J Exp Med. 2005 Aug 1;202(3):425-35
references.pmid: 16061729
references.citation: Cancer Biol Ther. 2005 Oct;4(10):1104-12
references.pmid: 16096370
references.citation: Immunity. 2005 Dec;23(6):649-59
references.pmid: 16356862
references.citation: J Immunol. 2006 Jan 1;176(1):248-55
references.pmid: 16365416
references.citation: Proc Natl Acad Sci U S A. 2006 Jan 24;103(4):994-9
references.pmid: 16418289
references.citation: Nature. 2006 Oct 5;443(7111):578-81
references.pmid: 17006449
references.citation: Anticancer Res. 2006 Nov-Dec;26(6B):4115-24
references.pmid: 17201122