Pathogen-Induced Proapoptotic Phenotype and High CD95 (Fas) Expression Accompany a Suboptimal CD8(+) T-Cell Response: Reversal by Adenoviral Vaccine

Pathogen-Induced Proapoptotic Phenotype and High CD95 (Fas) Expression Accompany a Suboptimal CD8(+) T-Cell Response: Reversal by Adenoviral Vaccine

Author Vasconcelos, Jose Ronnie Carvalho de Autor UNIFESP Google Scholar
Bruna-Romero, Oscar Google Scholar
Araujo, Adriano F. Autor UNIFESP Google Scholar
Dominguez, Mariana R. Autor UNIFESP Google Scholar
Ersching, Jonatan Autor UNIFESP Google Scholar
Alencar, Bruna C. G. de Autor UNIFESP Google Scholar
Machado, Alexandre V. Google Scholar
Gazzinelli, Ricardo T. Google Scholar
Bortoluci, Karina R. Autor UNIFESP Google Scholar
Amarante-Mendes, Gustavo P. Google Scholar
Lopes, Marcela F. Google Scholar
Rodrigues, Mauricio Martins Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Universidade Federal de Minas Gerais (UFMG)
Fiocruz MS
Univ Massachusetts
Universidade de São Paulo (USP)
Universidade Federal do Rio de Janeiro (UFRJ)
Abstract MHC class la-restricted CD8(+) T cells are important mediators of the adaptive immune response against infections caused by intracellular microorganisms. Whereas antigen-specific effector CD8(+) T cells can clear infection caused by intracellular pathogens, in some circumstances, the immune response is suboptimal and the microorganisms survive, causing host death or chronic infection. Here, we explored the cellular and molecular mechanisms that could explain why CD8(+) T-cell-mediated immunity during infection with the human protozoan parasite Trypanosoma cruzi is not optimal. for that purpose, we compared the CD8(+) T-cell mediated immune responses in mice infected with T. cruzi or vaccinated with a recombinant adenovirus expressing an immunodominant parasite antigen. Several functional and phenotypic characteristics of specific CD8(+) T cells overlapped. Among few exceptions was an accelerated expansion of the immune response in adenoviral vaccinated mice when compared to infected ones. Also, there was an upregulated expression of the apoptotic-signaling receptor CD95 on the surface of specific T cells from infected mice, which was not observed in the case of adenoviral-vaccinated mice. Most importantly, adenoviral vaccine provided at the time of infection significantly reduced the upregulation of CD95 expression and the proapoptotic phenotype of pathogen-specific CD8(+) cells expanded during infection. in parallel, infected adenovirus-vaccinated mice had a stronger CD8(+) T-cell mediated immune response and survived an otherwise lethal infection. We concluded that a suboptimal CD8(+) T-cell response is associated with an upregulation of CD95 expression and a proapoptotic phenotype. Both can be blocked by adenoviral vaccination.
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Millennium Institute for Gene Therapy (Brazil)
Grant number FAPESP: 2006/1983-4
FAPESP: 2009/06820-4
CNPq: 420067/2005-1
Date 2012-05-01
Published in Plos Pathogens. San Francisco: Public Library Science, v. 8, n. 5, 16 p., 2012.
ISSN 1553-7374 (Sherpa/Romeo, impact factor)
Publisher Public Library Science
Extent 16
Origin http://dx.doi.org/10.1371/journal.ppat.1002699
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000305322900033
URI http://repositorio.unifesp.br/handle/11600/34826

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