Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/7935
Title: Pathogen-induced proapoptotic phenotype and high CD95 (Fas) expression accompany a suboptimal CD8+ T-Cell response: reversal by adenoviral vaccine
Authors: Vasconcelos, José Ronnie
Araujo, Adriano Fernando da Silva
Dominguez, Mariana Ribeiro
Ersching, Jonatan
Bargieri, Bruna Cunha de Alencar
Bortoluci, Karina Ramalho
Rodrigues, Maurício Martins
Bruna-Romero, Oscar
Machado, Alexandre de Magalhaes Vieira
Gazzinelli, Ricardo Tostes
Mendes, João Gustavo Pessini Amarante
Lopes, Marcela de Freitas
Affilliation: Universidade Federal de São Paulo. Escola Paulista de Medicina. Centro de Terapia Celular e Molecular. São Paulo, SP, Brazil/Universidade Federal de São Paulo. Escola Paulista de Medicina. Departamento de Microbiologia, Imunologia e Parasitologia. São Paulo, SP, Brazil
Universidade Federal de São Paulo. Escola Paulista de Medicina. Centro de Terapia Celular e Molecular. São Paulo, SP, Brazil/Universidade Federal de São Paulo. Escola Paulista de Medicina. Departamento de Microbiologia, Imunologia e Parasitologia. São Paulo, SP, Brazil
Universidade Federal de São Paulo. Escola Paulista de Medicina. Centro de Terapia Celular e Molecular. São Paulo, SP, Brazil/Universidade Federal de São Paulo. Escola Paulista de Medicina. Departamento de Microbiologia, Imunologia e Parasitologia. São Paulo, SP, Brazil
Universidade Federal de São Paulo. Escola Paulista de Medicina. Centro de Terapia Celular e Molecular. São Paulo, SP, Brazil/Universidade Federal de São Paulo. Escola Paulista de Medicina. Departamento de Microbiologia, Imunologia e Parasitologia. São Paulo, SP, Brazil
Universidade Federal de São Paulo. Escola Paulista de Medicina. Centro de Terapia Celular e Molecular. São Paulo, SP, Brazil/Universidade Federal de São Paulo. Escola Paulista de Medicina. Departamento de Microbiologia, Imunologia e Parasitologia. São Paulo, SP, Brazil
Universidade Federal de São Paulo. Escola Paulista de Medicina. Centro de Terapia Celular e Molecular. São Paulo, SP, Brazil/Universidade Federal de São Paulo. Escola Paulista de Medicina. Departamento de Ciências Biológicas. Diadema, SP, Brazil
Universidade Federal de São Paulo. Escola Paulista de Medicina. Centro de Terapia Celular e Molecular. São Paulo, SP, Brazil/Universidade Federal de São Paulo. Escola Paulista de Medicina. Departamento de Microbiologia, Imunologia e Parasitologia. São Paulo, SP, Brazil
Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Microbiologia. Belo Horizonte, MG, Brazil
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brazil/Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brazil/University of Massachusetts. Medical School. Department of Medicine. Division of Infectious Disease and Immunology. Worcester, MA, United States of America
Universidade de São Paulo. Instituto de Ciências Biomédicas. Departamento de Imunologia. São Paulo, SP, Brazil
Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brazil
Abstract: MHC class Ia-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.
Keywords: Parasitic diseases
Protozoan infections
T cells
Trypanosoma cruzi
Issue Date: 2012
Publisher: Public Library of Science
Citation: VASCONCELOS, José Ronnie et al. Pathogen-induced proapoptotic phenotype and high CD95 (Fas) expression accompany a suboptimal CD8+ T-Cell response: reversal by adenoviral vaccine. Plos Pathogens. 2012, vol.8, pp. e1002699.
ISSN: 1553-7366
Copyright: open access
Appears in Collections:MG - IRR - Artigos de Periódicos



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