title: CD8(+) T cell-mediated immunity during Trypanosoma cruzi infection: a path for vaccine development?
abstract: MHC-restricted CD8(+) T cells are important during infection with the intracellular protozoan parasite Trypanosoma cruzi, the causative agent of Chagas disease. Experimental studies performed in the past 25 years have elucidated a number of features related to the immune response mediated by these T cells, which are important for establishing the parasite/host equilibrium leading to chronic infection. CD8(+) T cells are specific for highly immunodominant antigens expressed by members of the trans-sialidase family. After infection, their activation is delayed, and the cells display a high proliferative activity associated with high apoptotic rates. Although they participate in parasite control and elimination, they are unable to clear the infection due to their low fitness, allowing the parasite to establish the chronic phase when these cells then play an active role in the induction of heart immunopathology. Vaccination with a number of subunit recombinant vaccines aimed at eliciting specific CD8(+) T cells can reverse this path, thereby generating a productive immune response that will lead to the control of infection, reduction of symptoms, and reduction of disease transmission. Due to these attributes, activation of CD8(+) T lymphocytes may constitute a path for the development of a veterinarian or human vaccine.
authors.affiliation: Centro de Terapia Celular e Molecular (CTCMol), UNIFESP-Escola Paulista de Medicina, Rua Mirassol 207, São Paulo 04044-010, SP, Brazil ; Departmento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo-Escola Paulista de Medicina, Rua Mirassol 207, São Paulo 04044-010, SP, Brazil.
authors.forename: Fernando
authors.initials: F
authors.lastname: Dos Santos Virgilio
authors.affiliation: Centro de Terapia Celular e Molecular (CTCMol), UNIFESP-Escola Paulista de Medicina, Rua Mirassol 207, São Paulo 04044-010, SP, Brazil ; Departmento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo-Escola Paulista de Medicina, Rua Mirassol 207, São Paulo 04044-010, SP, Brazil.
authors.forename: Camila
authors.initials: C
authors.lastname: Pontes
authors.affiliation: Centro de Terapia Celular e Molecular (CTCMol), UNIFESP-Escola Paulista de Medicina, Rua Mirassol 207, São Paulo 04044-010, SP, Brazil ; Departmento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo-Escola Paulista de Medicina, Rua Mirassol 207, São Paulo 04044-010, SP, Brazil.
authors.forename: Mariana Ribeiro
authors.initials: MR
authors.lastname: Dominguez
authors.affiliation: Centro de Terapia Celular e Molecular (CTCMol), UNIFESP-Escola Paulista de Medicina, Rua Mirassol 207, São Paulo 04044-010, SP, Brazil ; Departmento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo-Escola Paulista de Medicina, Rua Mirassol 207, São Paulo 04044-010, SP, Brazil.
authors.forename: Jonatan
authors.initials: J
authors.lastname: Ersching
authors.affiliation: Centro de Terapia Celular e Molecular (CTCMol), UNIFESP-Escola Paulista de Medicina, Rua Mirassol 207, São Paulo 04044-010, SP, Brazil ; Departmento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo-Escola Paulista de Medicina, Rua Mirassol 207, São Paulo 04044-010, SP, Brazil.
authors.forename: Mauricio Martins
authors.initials: MM
authors.lastname: Rodrigues
authors.affiliation: Centro de Terapia Celular e Molecular (CTCMol), UNIFESP-Escola Paulista de Medicina, Rua Mirassol 207, São Paulo 04044-010, SP, Brazil ; Departmento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo-Escola Paulista de Medicina, Rua Mirassol 207, São Paulo 04044-010, SP, Brazil ; Departamento de Biociências, Instituto de Saúde e Sociedade, UNIFESP, Campus Baixada Santista, Santos 11015-020, SP, Brazil.
authors.forename: José Ronnie
authors.initials: JR
authors.lastname: Vasconcelos
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D014355:Chagas Disease / Q000276:immunology / Q000517:prevention & control; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology*; D014349:Trypanosoma cruzi / Q000276:immunology*; D014612:Vaccines / Q000276:immunology*
chemical_list: D014612:Vaccines
references.citation: J Cell Sci. 2000 Apr;113 ( Pt 7):1299-307
references.pmid: 10704380
references.citation: Nat Immunol. 2002 Jan;3(1):9-10
references.pmid: 11753400
references.citation: J Immunol. 2003 Dec 15;171(12):6344-8
references.pmid: 14662831
references.citation: J Immunol. 1993 Feb 15;150(4):1611-8
references.pmid: 8432996
references.citation: Nature. 2010 Jun 24;465(7301):S10-1
references.pmid: 20571547
references.citation: PLoS Pathog. 2012;8(5):e1002699
references.pmid: 22615561
references.citation: Clin Vaccine Immunol. 2008 Aug;15(8):1292-300
references.pmid: 18579696
references.citation: PLoS One. 2013;8(3):e59434
references.pmid: 23555672
references.citation: J Infect Dis. 2004 Mar 1;189(5):909-18
references.pmid: 14976609
references.citation: J Infect Dis. 2002 Sep 15;186(6):872-5
references.pmid: 12198628
references.citation: Nature. 2010 Jun 24;465(7301):S6-7
references.pmid: 20571554
references.citation: Parasitol Int. 2008 Mar;57(1):38-48
references.pmid: 17728174
references.citation: Infect Immun. 2006 Apr;74(4):2477-81
references.pmid: 16552083
references.citation: Vaccine. 2008 May 2;26(19):2322-34
references.pmid: 18403070
references.citation: Infect Immun. 2011 May;79(5):2120-30
references.pmid: 21357719
references.citation: Immunity. 2013 Jun 27;38(6):1250-60
references.pmid: 23746652
references.citation: Expert Rev Mol Med. 2010 Sep 15;12:e29
references.pmid: 20840799
references.citation: Curr Opin Infect Dis. 2008 Jun;21(3):287-92
references.pmid: 18448974
references.citation: Infect Immun. 2005 Nov;73(11):7356-65
references.pmid: 16239534
references.citation: Microbes Infect. 2005 Apr;7(4):688-97
references.pmid: 15848276
references.citation: Infect Immun. 2002 Sep;70(9):4833-40
references.pmid: 12183527
references.citation: Bioengineered. 2012 Jul-Aug;3(4):242-6
references.pmid: 22705838
references.citation: J Immunol. 2008 Feb 1;180(3):1737-48
references.pmid: 18209071
references.citation: Infect Immun. 2003 May;71(5):2744-57
references.pmid: 12704149
references.citation: Infect Immun. 2001 Sep;69(9):5477-86
references.pmid: 11500420
references.citation: Immunity. 2006 Oct;25(4):533-43
references.pmid: 17046682
references.citation: J Immunol. 2007 Nov 15;179(10):6889-900
references.pmid: 17982080
references.citation: Cardiovasc Res. 2003 Oct 15;60(1):96-107
references.pmid: 14522411
references.citation: Infect Immun. 1999 Aug;67(8):3855-63
references.pmid: 10417149
references.citation: Trends Parasitol. 2006 Dec;22(12):583-8
references.pmid: 17049308
references.citation: Braz J Med Biol Res. 2009 Mar;42(3):220-3
references.pmid: 19287899
references.citation: Clin Vaccine Immunol. 2008 Aug;15(8):1158-64
references.pmid: 18550728
references.citation: PLoS Negl Trop Dis. 2010 Dec 14;4(12):e916
references.pmid: 21179503
references.citation: Immunol Res. 2004;29(1-3):151-60
references.pmid: 15181278
references.citation: Vaccine. 1998 May;16(8):768-74
references.pmid: 9627933
references.citation: Proc Natl Acad Sci U S A. 2004 Feb 17;101(7):1916-21
references.pmid: 14769938
references.citation: Vaccine. 2007 Aug 10;25(32):6018-27
references.pmid: 17629597
references.citation: Virchows Arch A Pathol Anat Histopathol. 1993;423(3):157-60
references.pmid: 7901937
references.citation: Infect Immun. 2003 Mar;71(3):1185-93
references.pmid: 12595431
references.citation: Infect Immun. 1998 Nov;66(11):5073-81
references.pmid: 9784506
references.citation: PLoS Negl Trop Dis. 2008;2(9):e288
references.pmid: 18846233
references.citation: PLoS Pathog. 2012;8(4):e1002645
references.pmid: 22532799
references.citation: J Immunol. 1991 Apr 1;146(7):2394-400
references.pmid: 1706399
references.citation: Infect Immun. 2000 Sep;68(9):4986-91
references.pmid: 10948115
references.citation: Infect Immun. 2005 Dec;73(12):7960-6
references.pmid: 16299288
references.citation: Hum Vaccin. 2011 Nov;7(11):1184-91
references.pmid: 22048121
references.citation: Biol Res. 2010;43(3):323-31
references.pmid: 21249304
references.citation: PLoS Negl Trop Dis. 2011;5(5):e992
references.pmid: 21655351
references.citation: J Infect Dis. 2013 Feb 15;207(4):661-5
references.pmid: 23204182
references.citation: Expert Rev Vaccines. 2012 Sep;11(9):1043-55
references.pmid: 23151163
references.citation: Clin Exp Immunol. 2000 Sep;121(3):499-505
references.pmid: 10971517
references.citation: J Infect Dis. 2010 Jul 1;202(1):136-44
references.pmid: 20497050
references.citation: J Immunol. 2009 Jul 15;183(2):1245-52
references.pmid: 19553540
references.citation: PLoS Pathog. 2006 Aug;2(8):e77
references.pmid: 16879036
references.citation: J Immunol. 2010 Feb 1;184(3):1148-52
references.pmid: 20042586
references.citation: PLoS One. 2013 Apr 24;8(4):e61795
references.pmid: 23637908
references.citation: Infect Immun. 2002 Oct;70(10):5547-55
references.pmid: 12228281
references.citation: J Infect Dis. 2006 May 15;193(10):1394-9
references.pmid: 16619187
references.citation: Infect Immun. 2009 Oct;77(10):4383-95
references.pmid: 19651871
references.citation: Eur J Immunol. 2003 Jan;33(1):70-8
references.pmid: 12594834
references.citation: Vaccine. 2012 Apr 16;30(18):2882-91
references.pmid: 22381075
references.citation: Immunol Lett. 2006 Mar 15;103(2):186-91
references.pmid: 16378645
references.citation: PLoS One. 2007 Apr 25;2(4):e393
references.pmid: 17460760
references.citation: Vaccine. 2009 Oct 19;27(44):6154-9
references.pmid: 19712768
references.citation: PLoS One. 2012;7(5):e35966
references.pmid: 22574131
references.citation: Infect Immun. 2005 Sep;73(9):6017-25
references.pmid: 16113322
references.citation: Trends Parasitol. 2003 Oct;19(10):447-51
references.pmid: 14519582
references.citation: Adv Parasitol. 2011;75:121-46
references.pmid: 21820554
references.citation: Int Immunol. 1996 Jan;8(1):13-22
references.pmid: 8671585
references.citation: Hum Gene Ther. 2004 Sep;15(9):878-86
references.pmid: 15353042
references.citation: J Cell Mol Med. 2010 Jun;14(6B):1373-84
references.pmid: 20070438
references.citation: Cell Microbiol. 2014 Sep;16(9):1285-300
references.pmid: 24712539
references.citation: Infect Immun. 2014 Apr;82(4):1382-9
references.pmid: 24421046
references.citation: J Parasitol Res. 2012;2012:507874
references.pmid: 22496959
references.citation: Infect Immun. 2008 Jan;76(1):324-33
references.pmid: 17967857
references.citation: J Infect Dis. 2009 Feb 1;199(3):451-4
references.pmid: 19099482
references.citation: Microbes Infect. 2007 Jul;9(8):1011-9
references.pmid: 17548222
references.citation: Int Immunol. 2006 Mar;18(3):465-71
references.pmid: 16431876
references.citation: Front Immunol. 2012 Dec 04;3:358
references.pmid: 23264773
references.citation: Nat Med. 2008 May;14(5):542-50
references.pmid: 18425131
references.citation: Hum Gene Ther. 2014 Apr;25(4):350-63
references.pmid: 24568548
references.citation: Vaccine. 2003 Jun 20;21(21-22):3070-80
references.pmid: 12798651
references.citation: Infect Immun. 2004 Jan;72(1):46-53
references.pmid: 14688079
references.citation: J Immunol. 1997 Apr 1;158(7):3293-302
references.pmid: 9120286
references.citation: Am J Trop Med Hyg. 2004 Nov;71(5):594-7
references.pmid: 15569790
references.citation: Infect Immun. 2001 Oct;69(10):6558-63
references.pmid: 11553607
references.citation: Nat Immunol. 2003 Mar;4(3):225-34
references.pmid: 12563257
references.citation: Curr Opin Immunol. 2007 Aug;19(4):430-4
references.pmid: 17651955
references.citation: Hum Gene Ther. 2006 Sep;17(9):898-908
references.pmid: 16972758
references.citation: PLoS One. 2011;6(7):e22011
references.pmid: 21779365
references.citation: Am J Trop Med Hyg. 1994 Mar;50(3):261-8
references.pmid: 8147485
references.citation: PLoS One. 2013;8(3):e59347
references.pmid: 23527169
references.citation: Expert Rev Vaccines. 2009 Jul;8(7):921-35
references.pmid: 19538117