| Author | Alencar, Bruna C. G. de | |
| Author | Persechini, Pedro M. | |
| Author | Haolla, Filipe A. | |
| Author | Oliveira, Gabriel de | |
| Author | Silverio, Jaline C. | |
| Author | Lannes-Vieira, Joseli | |
| Author | Machado, Alexandre V. | |
| Author | Gazzinelli, Ricardo T. | |
| Author | Bruna-Romero, Oscar | |
| Author | Rodrigues, Mauricio M. | |
| Access date | 2017-08-29T14:12:36Z | |
| Available date | 2017-08-29T14:12:36Z | |
| Document date | 2009 | |
| Citation | ALENCAR, Bianca C. G. de; et al. Perforin and Gamma Interferon Expression Are Required for CD4 and CD8 T-Cell-Dependent Protective Immunity against a Human Parasite, Trypanosoma cruzi, Elicited by Heterologous Plasmid DNA Prime-Recombinant Adenovirus 5 Boost Vaccination. Infection and Immunity, v.77, n.10, p.4383-4395, Oct. 2009. | pt_BR |
| ISSN | 0019-9567 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/20807 | |
| Language | eng | pt_BR |
| Publisher | American Society for Microbiology | pt_BR |
| Rights | open access | |
| Subject in Portuguese | Trypanosoma cruzi | pt_BR |
| Subject in Portuguese | Perforina | pt_BR |
| Subject in Portuguese | Imunidade | pt_BR |
| Title | Perforin and gamma interferon expression are required for CD4+ and CD8+ T-cell-dependent protective immunity against a human parasite, Trypanosoma cruzi, elicited by heterologous plasmid DNA prime-recombinant adenovirus 5 boost vaccination | pt_BR |
| Type | Article | |
| Abstract | A heterologous prime-boost strategy using plasmid DNA, followed by replication-defective recombinant adenovirus 5, is being proposed as a powerful way to elicit CD4(+) and CD8(+) T-cell-mediated protective immunity against intracellular pathogens. We confirmed this concept and furthered existing research by providing evidence that the heterologous prime-boost regimen using the gene encoding amastigote surface protein 2 elicited CD4(+) and CD8(+) T-cell-mediated protective immunity (reduction of acute parasitemia and prolonged survival) against experimental infection with Trypanosoma cruzi. Protective immunity correlated with the presence of in vivo antigen-specific cytotoxic activity prior to challenge. Based on this, our second goal was to determine the outcome of infection after heterologous prime-boost immunization of perforin-deficient mice. These mice were highly susceptible to infection. A detailed analysis of the cell-mediated immune responses in immunized perforin-deficient mice showed an impaired gamma interferon (IFN-gamma) secretion by immune spleen cells upon restimulation in vitro with soluble recombinant antigen. In spite of a normal numeric expansion, specific CD8(+) T cells presented several functional defects detected in vivo (cytotoxicity) and in vitro (simultaneous expression of CD107a/IFN-gamma or IFN-gamma/tumor necrosis factor alpha) paralleled by a decreased expression of CD44 and KLRG-1. Our final goal was to determine the importance of IFN-gamma in the presence of highly cytotoxic T cells. Vaccinated IFN-gamma-deficient mice developed highly cytotoxic cells but failed to develop any protective immunity. Our study thus demonstrated a role for perforin and IFN-gamma in a number of T-cell-mediated effector functions and in the antiparasitic immunity generated by a heterologous plasmid DNA prime-adenovirus boost vaccination strategy. | pt_BR |
| Affilliation | Universidade Federal de São Paulo. Escola Paulista de Medicina. Centro Interdisciplinar de Terapia Gênica. São Paulo, SP, Brasil / Universidade Federal de São Paulo. Escola Paulista de Medicina. Departamento de Microbiologia, Imunologia e Parasitologia. São Paulo, SP, Brasil. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Centro de Ciências da Saúde. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal de São Paulo. Escola Paulista de Medicina. Centro Interdisciplinar de Terapia Gênica. São Paulo, SP, Brasil / Universidade Federal de São Paulo. Escola Paulista de Medicina. Departamento de Microbiologia, Imunologia e Parasitologia. São Paulo, SP, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular e Biologia das Interações. Rio de Janeiro, RJ. Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular e Biologia das Interações. Rio de Janeiro, RJ. Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular e Biologia das Interações. Rio de Janeiro, RJ. Brasil. | pt_BR |
| Affilliation | Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brasil. | pt_BR |
| Affilliation | Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brasil / University of Massachusetts Medical School. Department of Medicine. Division of Infectious Disease and Immunology. Worcester, Massachussets, USA. | pt_BR |
| Affilliation | Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Microbiologia. Belo Horizonte, MG, Brasil. | pt_BR |
| Affilliation | Universidade Federal de São Paulo. Escola Paulista de Medicina. Centro Interdisciplinar de Terapia Gênica. São Paulo, SP, Brasil / Universidade Federal de São Paulo. Escola Paulista de Medicina. Departamento de Microbiologia, Imunologia e Parasitologia. São Paulo, SP, Brasil. | pt_BR |
| Subject | Trypanosoma cruzi | pt_BR |
| Subject | Perforin | pt_BR |
| Subject | CD8 T-Cell | pt_BR |
| Subject | immunity | pt_BR |
| Subject | infection | pt_BR |
| e-ISSN | 10.1128/IAI.01459-08 | |
| e-ISSN | 1098-5522 | |
