CD8(+) T-Cells Expressing Interferon Gamma or Perforin Play Antagonistic Roles in Heart Injury in Experimental Trypanosoma Cruzi-Elicited Cardiomyopathy

CD8(+) T-Cells Expressing Interferon Gamma or Perforin Play Antagonistic Roles in Heart Injury in Experimental Trypanosoma Cruzi-Elicited Cardiomyopathy

Author Silverio, Jaline Coutinho Google Scholar
Pereira, Isabela Resende Google Scholar
Cipitelli, Marcio da Costa Google Scholar
Vinagre, Nathalia Ferreira Google Scholar
Rodrigues, Mauricio Martins Autor UNIFESP Google Scholar
Gazzinelli, Ricardo Tostes Google Scholar
Lannes-Vieira, Joseli Google Scholar
Institution Inst Oswaldo Cruz
Universidade Federal de São Paulo (UNIFESP)
Inst Rene Rachou
Universidade Federal de Minas Gerais (UFMG)
Abstract In Chagas disease, CD8(+) T-cells are critical for the control of Trypanosoma cruzi during acute infection. Conversely, CD8(+) T-cell accumulation in the myocardium during chronic infection may cause tissue injury leading to chronic chagasic cardiomyopathy (CCC). Here we explored the role of CD8(+) T-cells in T. cruzi-elicited heart injury in C57BL/6 mice infected with the Colombian strain. Cardiomyocyte lesion evaluated by creatine kinase-MB isoenzyme activity levels in the serum and electrical abnormalities revealed by electrocardiogram were not associated with the intensity of heart parasitism and myocarditis in the chronic infection. Further, there was no association between heart injury and systemic anti-T. cruzi CD8(+) T-cell capacity to produce interferon-gamma (IFN gamma) and to perform specific cytotoxicity. Heart injury, however, paralleled accumulation of anti-T. cruzi cells in the cardiac tissue. in T. cruzi infection, most of the CD8(+) T-cells segregated into IFN gamma(+) perforin (Pfn)(neg) or IFN gamma(neg)Pfn(+) cell populations. Colonization of the cardiac tissue by anti-T. cruzi CD8(+)Pfn(+) cells paralleled the worsening of CCC. the adoptive cell transfer to T. cruzi-infected cd8(-/-) recipients showed that the CD8(+) cells from infected ifn gamma(-/-) pfn(+/+) donors migrate towards the cardiac tissue to a greater extent and caused a more severe cardiomyocyte lesion than CD8(+) cells from ifn gamma(+/+) pfn(-/-) donors. Moreover, the reconstitution of naive cd8(-/-) mice with CD8(+) cells from naive ifn gamma(+/+) pfn(-/-) donors ameliorated T. cruzi-elicited heart injury paralleled IFN gamma(+) cells accumulation, whereas reconstitution with CD8(+) cells from naive ifn gamma(-/-) pfn(+/+) donors led to an aggravation of the cardiomyocyte lesion, which was associated with the accumulation of Pfn(+) cells in the cardiac tissue. Our data support a possible antagonist effect of CD8(+) Pfn(+) and CD8(+)IFN gamma(+) cells during CCC. CD8(+)IFN gamma(+) cells may exert a beneficial role, whereas CD8(+)Pfn(+) may play a detrimental role in T. cruzi-elicited heart injury.
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Grant number FAPERJ: APQ1-E-26/111.756/2008
FAPERJ: CNE/E-26/101.549/2010
CNPq: 471518/2006-9-Universal
CNPq: 302534/2008-3
Date 2012-04-01
Published in Plos Pathogens. San Francisco: Public Library Science, v. 8, n. 4, 20 p., 2012.
ISSN 1553-7374 (Sherpa/Romeo, impact factor)
Publisher Public Library Science
Extent 20
Origin http://dx.doi.org/10.1371/journal.ppat.1002645
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000303444200037
URI http://repositorio.unifesp.br/handle/11600/34735

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