Adenovirus vector-induced CD8⁺ T effector memory cell differentiation and recirculation, but not proliferation, are important for protective immunity against experimental Trypanosoma cruzi Infection.

Detalhes bibliográficos
Autor(a) principal: Vasconcelos, Jose Ronnie
Data de Publicação: 2014
Outros Autores: Dominguez, Mariana Ribeiro, Neves, Ramon Lemos, Ersching, Jonatan, Araujo, Adriano, Santos, Luara Isabela dos, Virgilio, Fernando dos Santos, Machado, Alexandre Vieira, Romero, Oscar Bruna, Gazzinelli, Ricardo Tostes, Rodrigues, Mauricio Martins
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/9482
Resumo: Universidade Federal de Sao Paulo. Escola Paulista de Medicina. Centro de Terapia Celular e Molecular. Sao Paulo, SP, Brazil/Universidade Federal de Sao Paulo. Escola Paulista de Medicina. Departamento de Microbiologia, Imunologia e Parasitologia. Sao Paulo, SP, Brazil/ Universidade Federal de Sao Paulo. Instituto de Saude e Sociedade. Departamento de Biociencias. Santos, SP, Brasil
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spelling Vasconcelos, Jose RonnieDominguez, Mariana RibeiroNeves, Ramon LemosErsching, JonatanAraujo, AdrianoSantos, Luara Isabela dosVirgilio, Fernando dos SantosMachado, Alexandre VieiraRomero, Oscar BrunaGazzinelli, Ricardo TostesRodrigues, Mauricio Martins2015-02-10T18:28:21Z2015-02-10T18:28:21Z2014VASCONCELOS, Jose Ronnie. Adenovirus vector-induced CD8⁺ T effector memory cell differentiation and recirculation, but not proliferation, are important for protective immunity against experimental Trypanosoma cruzi Infection. Hum Gene Ther , v. 25, n. 4, p. 350-363, 2014.1043-0342https://www.arca.fiocruz.br/handle/icict/948210.1089/hum.2013.218.engLiebertAdenovirus vector-induced CD8⁺ T effector memory cell differentiation and recirculation, but not proliferation, are important for protective immunity against experimental Trypanosoma cruzi Infection.info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleUniversidade Federal de Sao Paulo. Escola Paulista de Medicina. Centro de Terapia Celular e Molecular. Sao Paulo, SP, Brazil/Universidade Federal de Sao Paulo. Escola Paulista de Medicina. Departamento de Microbiologia, Imunologia e Parasitologia. Sao Paulo, SP, Brazil/ Universidade Federal de Sao Paulo. Instituto de Saude e Sociedade. Departamento de Biociencias. Santos, SP, BrasilUniversidade Federal de Sao Paulo. Escola Paulista de Medicina. Centro de Terapia Celular e Molecular. Sao Paulo, SP, Brazil/Universidade Federal de Sao Paulo. Escola Paulista de Medicina. Departamento de Microbiologia, Imunologia e Parasitologia. Sao Paulo, SP, Brazil.Universidade Federal de Sao Paulo. Escola Paulista de Medicina. Centro de Terapia Celular e Molecular. Sao Paulo, SP, Brazil/ Universidade Federal de Sao Paulo. Escola Paulista de Medicina. Departamento de Microbiologia, Imunologia e Parasitologia. Sao Paulo, SP, Brazil.Universidade Federal de Sao Paulo. Escola Paulista de Medicina. Centro de Terapia Celular e Molecular. Sao Paulo, SP, Brazil/ Universidade Federal de Sao Paulo. Escola Paulista de Medicina. Departamento de Microbiologia, Imunologia e Parasitologia. Sao Paulo, SP,Brazil.Universidade Federal de Sao Paulo. Escola Paulista de Medicina. Centro de Terapia Celular e Molecular. Sao Paulo, SP, Brazil/ Universidade Federal de Sao Paulo. Escola Paulista de Medicina. Departamento de Microbiologia, Imunologia e Parasitologia. Sao Paulo, SP, Brazil.Universidade Federal de Minas Gerais. Instituto de Ciencias Biologicas. Departamento de Bioquımica e Imunologia. Belo Horizonte, MG, Brazil.Universidade Federal de Sao Paulo. Escola Paulista de Medicina. Centro de Terapia Celular e Molecular. Sao Paulo, SP, Brazil/ Universidade Federal de Sao Paulo. Escola Paulista de Medicina. Departamento de Microbiologia, Imunologia e Parasitologia. Sao Paulo, SP, Brazil.Fundação Oswaldo Cruz. Centro de Pesquisas Rene Rachou. Belo Horizonte, MG, Brazil.Universidade Federal de Santa Catarina. Departamento de Microbiologia, Imunologia e Parasitologia Florianopolis, SC,Brazil.Universidade Federal de Minas Gerais. Instituto de Ciencias Biologicas. Departamento de Bioquımica e Imunologia. Belo Horizonte, MG, Brazil/Fundação Oswaldo Cruz. Centro de Pesquisas Rene Rachou. Belo Horizonte, MG, Brazil/University of Massachusetts Medical School. Department of Medicine. Division of Infectious Disease and Immunology. Worcester, MA, United States of AmericaUniversidade Federal de Sao Paulo. Escola Paulista de Medicina. Centro de Terapia Celular e Molecular. Sao Paulo, SP, Brazil/Universidade Federal de Sao Paulo. Escola Paulista de Medicina. Departamento de Microbiologia, Imunologia e Parasitologia. Sao Paulo, SP, Brazil.Heterologous prime-boost vaccination using plasmid DNA followed by replication-defective adenovirus vector generates a large number of specific CD8⁺ T effector memory (TEM) cells that provide long-term immunity against a variety of pathogens. In the present study, we initially characterized the frequency, phenotype, and function of these T cells in vaccinated mice that were subjected to infectious challenge with the human protozoan parasite Trypanosoma cruzi. We observed that the frequency of the specific CD8⁺ T cells in the spleens of the vaccinated mice increased after challenge. Specific TEM cells differentiated into cells with a KLRG1(High) CD27(Low) CD43(Low) CD183(Low)T-bet(High) Eomes(Low) phenotype and capable to produce simultaneously the antiparasitic mediators IFNγ and TNF. Using the gzmBCreERT2/ROSA26EYFP transgenic mouse line, in which the cells that express Granzyme B after immunization, are indelibly labeled with enhanced yellow fluorescent protein, we confirmed that CD8⁺ T cells present after challenge were indeed TEM cells that had been induced by vaccination. Subsequently, we observed that the in vivo increase in the frequency of the specific CD8⁺ T cells was not because of an anamnestic immune response. Most importantly, after challenge, the increase in the frequency of specific cells and the protective immunity they mediate were insensitive to treatment with the cytostatic toxic agent hydroxyurea. We have previously described that the administration of the drug FTY720, which reduces lymphocyte recirculation, severely impairs protective immunity, and our evidence supports the model that when large amounts of antigen-experienced CD8⁺ TEM cells are present after heterologous prime-boost vaccination, differentiation, and recirculation, rather than proliferation, are key for the resultant protective immunity.CD8-Positive T-Lymphocytes/immunologyChagas Disease/prevention & controlGenetic Vectors/geneticsT-Cell Antigen Receptor Specificity/immunologyinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-81914https://www.arca.fiocruz.br/bitstream/icict/9482/1/license.txt7d48279ffeed55da8dfe2f8e81f3b81fMD51ORIGINAL2014_072.pdf2014_072.pdfapplication/pdf1105619https://www.arca.fiocruz.br/bitstream/icict/9482/2/2014_072.pdf1c4dff071e5f0a95c7f32f990bd748dcMD52TEXT2014_072.pdf.txt2014_072.pdf.txtExtracted texttext/plain57758https://www.arca.fiocruz.br/bitstream/icict/9482/3/2014_072.pdf.txte31ff6fa8cd45c660afd1d26b8e8db8cMD53icict/94822022-01-28 15:03:57.968oai:www.arca.fiocruz.br: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ório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352022-01-28T18:03:57Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false
dc.title.pt_BR.fl_str_mv Adenovirus vector-induced CD8⁺ T effector memory cell differentiation and recirculation, but not proliferation, are important for protective immunity against experimental Trypanosoma cruzi Infection.
title Adenovirus vector-induced CD8⁺ T effector memory cell differentiation and recirculation, but not proliferation, are important for protective immunity against experimental Trypanosoma cruzi Infection.
spellingShingle Adenovirus vector-induced CD8⁺ T effector memory cell differentiation and recirculation, but not proliferation, are important for protective immunity against experimental Trypanosoma cruzi Infection.
Vasconcelos, Jose Ronnie
CD8-Positive T-Lymphocytes/immunology
Chagas Disease/prevention & control
Genetic Vectors/genetics
T-Cell Antigen Receptor Specificity/immunology
title_short Adenovirus vector-induced CD8⁺ T effector memory cell differentiation and recirculation, but not proliferation, are important for protective immunity against experimental Trypanosoma cruzi Infection.
title_full Adenovirus vector-induced CD8⁺ T effector memory cell differentiation and recirculation, but not proliferation, are important for protective immunity against experimental Trypanosoma cruzi Infection.
title_fullStr Adenovirus vector-induced CD8⁺ T effector memory cell differentiation and recirculation, but not proliferation, are important for protective immunity against experimental Trypanosoma cruzi Infection.
title_full_unstemmed Adenovirus vector-induced CD8⁺ T effector memory cell differentiation and recirculation, but not proliferation, are important for protective immunity against experimental Trypanosoma cruzi Infection.
title_sort Adenovirus vector-induced CD8⁺ T effector memory cell differentiation and recirculation, but not proliferation, are important for protective immunity against experimental Trypanosoma cruzi Infection.
author Vasconcelos, Jose Ronnie
author_facet Vasconcelos, Jose Ronnie
Dominguez, Mariana Ribeiro
Neves, Ramon Lemos
Ersching, Jonatan
Araujo, Adriano
Santos, Luara Isabela dos
Virgilio, Fernando dos Santos
Machado, Alexandre Vieira
Romero, Oscar Bruna
Gazzinelli, Ricardo Tostes
Rodrigues, Mauricio Martins
author_role author
author2 Dominguez, Mariana Ribeiro
Neves, Ramon Lemos
Ersching, Jonatan
Araujo, Adriano
Santos, Luara Isabela dos
Virgilio, Fernando dos Santos
Machado, Alexandre Vieira
Romero, Oscar Bruna
Gazzinelli, Ricardo Tostes
Rodrigues, Mauricio Martins
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Vasconcelos, Jose Ronnie
Dominguez, Mariana Ribeiro
Neves, Ramon Lemos
Ersching, Jonatan
Araujo, Adriano
Santos, Luara Isabela dos
Virgilio, Fernando dos Santos
Machado, Alexandre Vieira
Romero, Oscar Bruna
Gazzinelli, Ricardo Tostes
Rodrigues, Mauricio Martins
dc.subject.en.pt_BR.fl_str_mv CD8-Positive T-Lymphocytes/immunology
Chagas Disease/prevention & control
Genetic Vectors/genetics
T-Cell Antigen Receptor Specificity/immunology
topic CD8-Positive T-Lymphocytes/immunology
Chagas Disease/prevention & control
Genetic Vectors/genetics
T-Cell Antigen Receptor Specificity/immunology
description Universidade Federal de Sao Paulo. Escola Paulista de Medicina. Centro de Terapia Celular e Molecular. Sao Paulo, SP, Brazil/Universidade Federal de Sao Paulo. Escola Paulista de Medicina. Departamento de Microbiologia, Imunologia e Parasitologia. Sao Paulo, SP, Brazil/ Universidade Federal de Sao Paulo. Instituto de Saude e Sociedade. Departamento de Biociencias. Santos, SP, Brasil
publishDate 2014
dc.date.issued.fl_str_mv 2014
dc.date.accessioned.fl_str_mv 2015-02-10T18:28:21Z
dc.date.available.fl_str_mv 2015-02-10T18:28:21Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
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dc.identifier.citation.fl_str_mv VASCONCELOS, Jose Ronnie. Adenovirus vector-induced CD8⁺ T effector memory cell differentiation and recirculation, but not proliferation, are important for protective immunity against experimental Trypanosoma cruzi Infection. Hum Gene Ther , v. 25, n. 4, p. 350-363, 2014.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/9482
dc.identifier.issn.none.fl_str_mv 1043-0342
dc.identifier.doi.none.fl_str_mv 10.1089/hum.2013.218.
identifier_str_mv VASCONCELOS, Jose Ronnie. Adenovirus vector-induced CD8⁺ T effector memory cell differentiation and recirculation, but not proliferation, are important for protective immunity against experimental Trypanosoma cruzi Infection. Hum Gene Ther , v. 25, n. 4, p. 350-363, 2014.
1043-0342
10.1089/hum.2013.218.
url https://www.arca.fiocruz.br/handle/icict/9482
dc.language.iso.fl_str_mv eng
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dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
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dc.publisher.none.fl_str_mv Liebert
publisher.none.fl_str_mv Liebert
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
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