Modulation of CD4(+) T Cell-Dependent Specific Cytotoxic CD8(+) T Cells Differentiation and Proliferation by the Timing of Increase in the Pathogen Load
Autor(a) principal: | |
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Data de Publicação: | 2007 |
Outros Autores: | , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNIFESP |
Texto Completo: | http://repositorio.unifesp.br/handle/11600/29673 http://dx.doi.org/10.1371/journal.pone.0000393 |
Resumo: | Background. Following infection with viruses, bacteria or protozoan parasites, naive antigen-specific CD8(+) T cells undergo a process of differentiation and proliferation to generate effector cells. Recent evidences suggest that the timing of generation of specific effector CD8(+) T cells varies widely according to different pathogens. We hypothesized that the timing of increase in the pathogen load could be a critical parameter governing this process. Methodology/Principal Findings. Using increasing doses of the protozoan parasite Trypanosoma cruzi to infect C57BL/6 mice, we observed a significant acceleration in the timing of parasitemia without an increase in mouse susceptibility. in contrast, in CD8 deficient mice, we observed an inverse relationship between the parasite inoculum and the timing of death. These results suggest that in normal mice CD8(+) T cells became protective earlier, following the accelerated development of parasitemia. the evaluation of specific cytotoxic responses in vivo to three distinct epitopes revealed that increasing the parasite inoculum hastened the expansion of specific CD8(+) cytotoxic T cells following infection. the differentiation and expansion of T. cruzi-specific CD8(+) cytotoxic T cells is in fact dependent on parasite multiplication, as radiation-attenuated parasites were unable to activate these cells. We also observed that, in contrast to most pathogens, the activation process of T. cruzi-specific CD8(+) cytotoxic T cells was dependent on MHC class II restricted CD4(+) T cells. Conclusions/Significance. Our results are compatible with our initial hypothesis that the timing of increase in the pathogen load can be a critical parameter governing the kinetics of CD4(+) T cell-dependent expansion of pathogen-specific CD8(+) cytotoxic T cells. |
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Tzelepis, Fanny [UNIFESP]Persechini, Pedro M.Rodrigues, Mauricio M. [UNIFESP]Universidade Federal de São Paulo (UNIFESP)Universidade Federal do Rio de Janeiro (UFRJ)2016-01-24T13:48:36Z2016-01-24T13:48:36Z2007-04-25Plos One. San Francisco: Public Library Science, v. 2, n. 4, 9 p., 2007.1932-6203http://repositorio.unifesp.br/handle/11600/29673http://dx.doi.org/10.1371/journal.pone.0000393WOS000207445600007.pdf10.1371/journal.pone.0000393WOS:000207445600007Background. Following infection with viruses, bacteria or protozoan parasites, naive antigen-specific CD8(+) T cells undergo a process of differentiation and proliferation to generate effector cells. Recent evidences suggest that the timing of generation of specific effector CD8(+) T cells varies widely according to different pathogens. We hypothesized that the timing of increase in the pathogen load could be a critical parameter governing this process. Methodology/Principal Findings. Using increasing doses of the protozoan parasite Trypanosoma cruzi to infect C57BL/6 mice, we observed a significant acceleration in the timing of parasitemia without an increase in mouse susceptibility. in contrast, in CD8 deficient mice, we observed an inverse relationship between the parasite inoculum and the timing of death. These results suggest that in normal mice CD8(+) T cells became protective earlier, following the accelerated development of parasitemia. the evaluation of specific cytotoxic responses in vivo to three distinct epitopes revealed that increasing the parasite inoculum hastened the expansion of specific CD8(+) cytotoxic T cells following infection. the differentiation and expansion of T. cruzi-specific CD8(+) cytotoxic T cells is in fact dependent on parasite multiplication, as radiation-attenuated parasites were unable to activate these cells. We also observed that, in contrast to most pathogens, the activation process of T. cruzi-specific CD8(+) cytotoxic T cells was dependent on MHC class II restricted CD4(+) T cells. Conclusions/Significance. Our results are compatible with our initial hypothesis that the timing of increase in the pathogen load can be a critical parameter governing the kinetics of CD4(+) T cell-dependent expansion of pathogen-specific CD8(+) cytotoxic T cells.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Millennium Institute for Vaccine Development and TechnologyConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Universidade Federal de São Paulo, Escola Paulista Med, CINTERGEN, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Microbiol Imunol & Parasitol, São Paulo, BrazilUniv Fed Rio de Janeiro, Inst Biofis Carlos Chagas Filho, Ilha Fundao, Ctr Ciencias Saude, BR-21941 Rio de Janeiro, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, CINTERGEN, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Microbiol Imunol & Parasitol, São Paulo, BrazilMillennium Institute for Vaccine Development and Technology: CNPq - 420067/2005-1Web of Science9engPublic Library SciencePlos OneModulation of CD4(+) T Cell-Dependent Specific Cytotoxic CD8(+) T Cells Differentiation and Proliferation by the Timing of Increase in the Pathogen Loadinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESPORIGINALWOS000207445600007.pdfapplication/pdf786862${dspace.ui.url}/bitstream/11600/29673/1/WOS000207445600007.pdfcb6137036e5148ddb3bf58f6179f4a29MD51open accessTEXTWOS000207445600007.pdf.txtWOS000207445600007.pdf.txtExtracted texttext/plain42594${dspace.ui.url}/bitstream/11600/29673/2/WOS000207445600007.pdf.txt9e49c87654567382eb51d418ee047c55MD52open access11600/296732022-06-02 10:26:54.498open accessoai:repositorio.unifesp.br:11600/29673Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestopendoar:34652023-05-25T12:17:18.256540Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.en.fl_str_mv |
Modulation of CD4(+) T Cell-Dependent Specific Cytotoxic CD8(+) T Cells Differentiation and Proliferation by the Timing of Increase in the Pathogen Load |
title |
Modulation of CD4(+) T Cell-Dependent Specific Cytotoxic CD8(+) T Cells Differentiation and Proliferation by the Timing of Increase in the Pathogen Load |
spellingShingle |
Modulation of CD4(+) T Cell-Dependent Specific Cytotoxic CD8(+) T Cells Differentiation and Proliferation by the Timing of Increase in the Pathogen Load Tzelepis, Fanny [UNIFESP] |
title_short |
Modulation of CD4(+) T Cell-Dependent Specific Cytotoxic CD8(+) T Cells Differentiation and Proliferation by the Timing of Increase in the Pathogen Load |
title_full |
Modulation of CD4(+) T Cell-Dependent Specific Cytotoxic CD8(+) T Cells Differentiation and Proliferation by the Timing of Increase in the Pathogen Load |
title_fullStr |
Modulation of CD4(+) T Cell-Dependent Specific Cytotoxic CD8(+) T Cells Differentiation and Proliferation by the Timing of Increase in the Pathogen Load |
title_full_unstemmed |
Modulation of CD4(+) T Cell-Dependent Specific Cytotoxic CD8(+) T Cells Differentiation and Proliferation by the Timing of Increase in the Pathogen Load |
title_sort |
Modulation of CD4(+) T Cell-Dependent Specific Cytotoxic CD8(+) T Cells Differentiation and Proliferation by the Timing of Increase in the Pathogen Load |
author |
Tzelepis, Fanny [UNIFESP] |
author_facet |
Tzelepis, Fanny [UNIFESP] Persechini, Pedro M. Rodrigues, Mauricio M. [UNIFESP] |
author_role |
author |
author2 |
Persechini, Pedro M. Rodrigues, Mauricio M. [UNIFESP] |
author2_role |
author author |
dc.contributor.institution.none.fl_str_mv |
Universidade Federal de São Paulo (UNIFESP) Universidade Federal do Rio de Janeiro (UFRJ) |
dc.contributor.author.fl_str_mv |
Tzelepis, Fanny [UNIFESP] Persechini, Pedro M. Rodrigues, Mauricio M. [UNIFESP] |
description |
Background. Following infection with viruses, bacteria or protozoan parasites, naive antigen-specific CD8(+) T cells undergo a process of differentiation and proliferation to generate effector cells. Recent evidences suggest that the timing of generation of specific effector CD8(+) T cells varies widely according to different pathogens. We hypothesized that the timing of increase in the pathogen load could be a critical parameter governing this process. Methodology/Principal Findings. Using increasing doses of the protozoan parasite Trypanosoma cruzi to infect C57BL/6 mice, we observed a significant acceleration in the timing of parasitemia without an increase in mouse susceptibility. in contrast, in CD8 deficient mice, we observed an inverse relationship between the parasite inoculum and the timing of death. These results suggest that in normal mice CD8(+) T cells became protective earlier, following the accelerated development of parasitemia. the evaluation of specific cytotoxic responses in vivo to three distinct epitopes revealed that increasing the parasite inoculum hastened the expansion of specific CD8(+) cytotoxic T cells following infection. the differentiation and expansion of T. cruzi-specific CD8(+) cytotoxic T cells is in fact dependent on parasite multiplication, as radiation-attenuated parasites were unable to activate these cells. We also observed that, in contrast to most pathogens, the activation process of T. cruzi-specific CD8(+) cytotoxic T cells was dependent on MHC class II restricted CD4(+) T cells. Conclusions/Significance. Our results are compatible with our initial hypothesis that the timing of increase in the pathogen load can be a critical parameter governing the kinetics of CD4(+) T cell-dependent expansion of pathogen-specific CD8(+) cytotoxic T cells. |
publishDate |
2007 |
dc.date.issued.fl_str_mv |
2007-04-25 |
dc.date.accessioned.fl_str_mv |
2016-01-24T13:48:36Z |
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2016-01-24T13:48:36Z |
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info:eu-repo/semantics/publishedVersion |
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dc.identifier.citation.fl_str_mv |
Plos One. San Francisco: Public Library Science, v. 2, n. 4, 9 p., 2007. |
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http://repositorio.unifesp.br/handle/11600/29673 http://dx.doi.org/10.1371/journal.pone.0000393 |
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1932-6203 |
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WOS000207445600007.pdf |
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10.1371/journal.pone.0000393 |
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WOS:000207445600007 |
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Plos One. San Francisco: Public Library Science, v. 2, n. 4, 9 p., 2007. 1932-6203 WOS000207445600007.pdf 10.1371/journal.pone.0000393 WOS:000207445600007 |
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http://repositorio.unifesp.br/handle/11600/29673 http://dx.doi.org/10.1371/journal.pone.0000393 |
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