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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Vasconcelos, Jose Ronnie [1, 2] ; Bruna-Romero, Oscar [3] ; Araujo, Adriano F. [2, 1] ; Dominguez, Mariana R. [2, 1] ; Ersching, Jonatan [1, 2] ; de Alencar, Bruna C. G. [1, 2] ; Machado, Alexandre V. [4] ; Gazzinelli, Ricardo T. [5, 4, 6] ; Bortoluci, Karina R. [2, 7] ; Amarante-Mendes, Gustavo P. [8] ; Lopes, Marcela F. [9] ; Rodrigues, Mauricio M. [1, 2]
Total Authors: 12
Affiliation:
[1] Univ Fed Sao Paulo, Dept Microbiol Imunol & Parasitol, Escola Paulista Med, Sao Paulo - Brazil
[2] Univ Fed Sao Paulo, Ctr Terapia Celular & Mol CTCMol, Escola Paulista Med, Sao Paulo - Brazil
[3] Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Microbiol, Belo Horizonte, MG - Brazil
[4] Fiocruz MS, Ctr Pesquisas Rene Rachou, Belo Horizonte, MG - Brazil
[5] Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Bioquim & Imunol, Belo Horizonte, MG - Brazil
[6] Univ Massachusetts, Sch Med, Dept Med, Div Infect Dis & Immunol, Worcester, MA - USA
[7] Univ Fed Sao Paulo, Dept Ciencias Biol, Escola Paulista Med, Sao Paulo - Brazil
[8] Univ Sao Paulo, Inst Ciencias Biomed, Dept Imunol, BR-05508 Sao Paulo - Brazil
[9] Univ Fed Rio de Janeiro, Inst Biofis Carlos Chagas Filho, BR-21941 Rio De Janeiro - Brazil
Total Affiliations: 9
Document type: Journal article
Source: PLOS PATHOGENS; v. 8, n. 5 MAY 2012.
Web of Science Citations: 41
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. (AU)

FAPESP's process: 09/06820-4 - Characterization of antigen presenting cells capable of initiating the immune response and control the immunodominance during Trypanosoma cruzi infection
Grantee:Maurício Martins Rodrigues
Support type: Regular Research Grants