Immune modulation induced by tuberculosis DNA vaccine protects non-obese diabetic mice from diabetes progression
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 UNESP |
Texto Completo: | http://dx.doi.org/10.1111/j.1365-2249.2007.03433.x http://hdl.handle.net/11449/37463 |
Resumo: | We have described previously the prophylactic and therapeutic effect of a DNA vaccine encoding the Mycobacterium leprae 65 kDa heat shock protein (DNA-HSP65) in experimental murine tuberculosis. However, the high homology of this protein to the corresponding mammalian 60 kDa heat shock protein (Hsp60), together with the CpG motifs in the plasmid vector, could trigger or exacerbate the development of autoimmune diseases. The non-obese diabetic (NOD) mouse develops insulin-dependent diabetes mellitus (IDDM) spontaneously as a consequence of an autoimmune process that leads to destruction of the insulin-producing beta cells of the pancreas. IDDM is characterized by increased T helper 1 (Th1) cell responses toward several autoantigens, including Hsp60, glutamic acid decarboxylase and insulin. In the present study, we evaluated the potential of DNA-HSP65 injection to modulate diabetes in NOD mice. Our results show that DNA-HSP65 or DNA empty vector had no diabetogenic effect and actually protected NOD mice against the development of severe diabetes. However, this effect was more pronounced in DNA-HSP65-injected mice. The protective effect of DNA-HSP65 injection was associated with a clear shift in the cellular infiltration pattern in the pancreas. This change included reduction of CD4(+) and CD8(+) T cells infiltration, appearance of CD25(+) cells influx and an increased staining for interleukin (IL)-10 in the islets. These results show that DNA-HSP65 can protect NOD mice against diabetes and can therefore be considered in the development of new immunotherapeutic strategies. |
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Immune modulation induced by tuberculosis DNA vaccine protects non-obese diabetic mice from diabetes progressioncytokinesdiabetesDNA vaccineheat shock protein (Hsp65)We have described previously the prophylactic and therapeutic effect of a DNA vaccine encoding the Mycobacterium leprae 65 kDa heat shock protein (DNA-HSP65) in experimental murine tuberculosis. However, the high homology of this protein to the corresponding mammalian 60 kDa heat shock protein (Hsp60), together with the CpG motifs in the plasmid vector, could trigger or exacerbate the development of autoimmune diseases. The non-obese diabetic (NOD) mouse develops insulin-dependent diabetes mellitus (IDDM) spontaneously as a consequence of an autoimmune process that leads to destruction of the insulin-producing beta cells of the pancreas. IDDM is characterized by increased T helper 1 (Th1) cell responses toward several autoantigens, including Hsp60, glutamic acid decarboxylase and insulin. In the present study, we evaluated the potential of DNA-HSP65 injection to modulate diabetes in NOD mice. Our results show that DNA-HSP65 or DNA empty vector had no diabetogenic effect and actually protected NOD mice against the development of severe diabetes. However, this effect was more pronounced in DNA-HSP65-injected mice. The protective effect of DNA-HSP65 injection was associated with a clear shift in the cellular infiltration pattern in the pancreas. This change included reduction of CD4(+) and CD8(+) T cells infiltration, appearance of CD25(+) cells influx and an increased staining for interleukin (IL)-10 in the islets. These results show that DNA-HSP65 can protect NOD mice against diabetes and can therefore be considered in the development of new immunotherapeutic strategies.Fac Med Ribeirao Preto, Dept Bioquim & Imunol, BR-14049900 Ribeirao Preto, SP, BrazilUNESP, Inst Biociencias, Botucatu, SP, BrazilUniv Estadual Campinas, Fac Ciências Med, Dept Clin Med, Lab Imunol Clin, Campinas, SP, BrazilUNESP, Inst Biociencias, Botucatu, SP, BrazilBlackwell PublishingUniversidade de São Paulo (USP)Universidade Estadual Paulista (Unesp)Universidade Estadual de Campinas (UNICAMP)dos Santos, R. RodriguesSartori, A.Bonato, V. L. DeperonCastelo, A. A. M. CoelhoVilella, C. A.Zollner, R. L.Silva, C. Lopes2014-05-20T15:27:30Z2014-05-20T15:27:30Z2007-09-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article570-578application/pdfhttp://dx.doi.org/10.1111/j.1365-2249.2007.03433.xClinical and Experimental Immunology. Oxford: Blackwell Publishing, v. 149, n. 3, p. 570-578, 2007.0009-9104http://hdl.handle.net/11449/3746310.1111/j.1365-2249.2007.03433.xWOS:000248978200021WOS000248978200021.pdf4977572416129527Web of Sciencereponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengClinical and Experimental Immunology3.5421,431info:eu-repo/semantics/openAccess2023-10-22T06:12:33Zoai:repositorio.unesp.br:11449/37463Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T15:39:52.347776Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Immune modulation induced by tuberculosis DNA vaccine protects non-obese diabetic mice from diabetes progression |
title |
Immune modulation induced by tuberculosis DNA vaccine protects non-obese diabetic mice from diabetes progression |
spellingShingle |
Immune modulation induced by tuberculosis DNA vaccine protects non-obese diabetic mice from diabetes progression dos Santos, R. Rodrigues cytokines diabetes DNA vaccine heat shock protein (Hsp65) |
title_short |
Immune modulation induced by tuberculosis DNA vaccine protects non-obese diabetic mice from diabetes progression |
title_full |
Immune modulation induced by tuberculosis DNA vaccine protects non-obese diabetic mice from diabetes progression |
title_fullStr |
Immune modulation induced by tuberculosis DNA vaccine protects non-obese diabetic mice from diabetes progression |
title_full_unstemmed |
Immune modulation induced by tuberculosis DNA vaccine protects non-obese diabetic mice from diabetes progression |
title_sort |
Immune modulation induced by tuberculosis DNA vaccine protects non-obese diabetic mice from diabetes progression |
author |
dos Santos, R. Rodrigues |
author_facet |
dos Santos, R. Rodrigues Sartori, A. Bonato, V. L. Deperon Castelo, A. A. M. Coelho Vilella, C. A. Zollner, R. L. Silva, C. Lopes |
author_role |
author |
author2 |
Sartori, A. Bonato, V. L. Deperon Castelo, A. A. M. Coelho Vilella, C. A. Zollner, R. L. Silva, C. Lopes |
author2_role |
author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade de São Paulo (USP) Universidade Estadual Paulista (Unesp) Universidade Estadual de Campinas (UNICAMP) |
dc.contributor.author.fl_str_mv |
dos Santos, R. Rodrigues Sartori, A. Bonato, V. L. Deperon Castelo, A. A. M. Coelho Vilella, C. A. Zollner, R. L. Silva, C. Lopes |
dc.subject.por.fl_str_mv |
cytokines diabetes DNA vaccine heat shock protein (Hsp65) |
topic |
cytokines diabetes DNA vaccine heat shock protein (Hsp65) |
description |
We have described previously the prophylactic and therapeutic effect of a DNA vaccine encoding the Mycobacterium leprae 65 kDa heat shock protein (DNA-HSP65) in experimental murine tuberculosis. However, the high homology of this protein to the corresponding mammalian 60 kDa heat shock protein (Hsp60), together with the CpG motifs in the plasmid vector, could trigger or exacerbate the development of autoimmune diseases. The non-obese diabetic (NOD) mouse develops insulin-dependent diabetes mellitus (IDDM) spontaneously as a consequence of an autoimmune process that leads to destruction of the insulin-producing beta cells of the pancreas. IDDM is characterized by increased T helper 1 (Th1) cell responses toward several autoantigens, including Hsp60, glutamic acid decarboxylase and insulin. In the present study, we evaluated the potential of DNA-HSP65 injection to modulate diabetes in NOD mice. Our results show that DNA-HSP65 or DNA empty vector had no diabetogenic effect and actually protected NOD mice against the development of severe diabetes. However, this effect was more pronounced in DNA-HSP65-injected mice. The protective effect of DNA-HSP65 injection was associated with a clear shift in the cellular infiltration pattern in the pancreas. This change included reduction of CD4(+) and CD8(+) T cells infiltration, appearance of CD25(+) cells influx and an increased staining for interleukin (IL)-10 in the islets. These results show that DNA-HSP65 can protect NOD mice against diabetes and can therefore be considered in the development of new immunotherapeutic strategies. |
publishDate |
2007 |
dc.date.none.fl_str_mv |
2007-09-01 2014-05-20T15:27:30Z 2014-05-20T15:27:30Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1111/j.1365-2249.2007.03433.x Clinical and Experimental Immunology. Oxford: Blackwell Publishing, v. 149, n. 3, p. 570-578, 2007. 0009-9104 http://hdl.handle.net/11449/37463 10.1111/j.1365-2249.2007.03433.x WOS:000248978200021 WOS000248978200021.pdf 4977572416129527 |
url |
http://dx.doi.org/10.1111/j.1365-2249.2007.03433.x http://hdl.handle.net/11449/37463 |
identifier_str_mv |
Clinical and Experimental Immunology. Oxford: Blackwell Publishing, v. 149, n. 3, p. 570-578, 2007. 0009-9104 10.1111/j.1365-2249.2007.03433.x WOS:000248978200021 WOS000248978200021.pdf 4977572416129527 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Clinical and Experimental Immunology 3.542 1,431 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
570-578 application/pdf |
dc.publisher.none.fl_str_mv |
Blackwell Publishing |
publisher.none.fl_str_mv |
Blackwell Publishing |
dc.source.none.fl_str_mv |
Web of Science reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
_version_ |
1808128546667757568 |