Increased frequency of CD4 and CD8 regulatory T cells in individuals under 15 years with multibacillary leprosy
Autor(a) principal: | |
---|---|
Data de Publicação: | 2013 |
Outros Autores: | , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da Universidade Federal do Ceará (UFC) |
Texto Completo: | http://www.repositorio.ufc.br/handle/riufc/8537 |
Resumo: | Background: Leprosy is a chronic disease, caused by Mycobacterium leprae, which poses a serious public health problem worldwide. Its high incidence in people under 15 years old in Ceara´ state, Brazil, reflects the difficulty of its control. The spectrum of clinical manifestations is associated with the immune response developed, with the Th1 and Th2 responses being related to the paucibacillary and multibacillary forms, respectively. Regulatory T cells (Treg), which can suppress Th1 and Th2 response, have received special attention in the literature and have been associated with development of chronic infections. However, their role in leprosy in individuals under 15 years old has not yet been elucidated. We evaluated the frequency of CD4+/CD8+CD25highFOXP3+ and CD4+/CD8+CD25highFOXP3high cells in leprosy patients and household contacts, in both cases under 15 years old. Methodology/Principal Findings: PBMC from 12 patients and 17 contacts were cultured for 72 hours with anti-CD3 and anti-CD28 (activators) or with activators associated with total sonicated fraction of M. leprae. After culture, the frequency of CD4+/CD8+ Treg was identified by flow cytometry. Cells stimulated by activators and antigen from multibacillary patients showed Treg frequencies almost two times that of the contacts: CD4+FOXP3+ (21.9368.43 vs. 13.7968.19%, p = 0.0500), CD4+FOXP3high (10.3365.69 vs. 5.5764.03%, p = 0.0362), CD8+FOXP3+ (13.8869.19 vs. 6.1865.56%, p = 0.0230) and CD8+FOXP3high (5.3664.17 vs. 2.2362.68%, p = 0.0461). Furthermore, the mean fluorescence intensity of FOXP3 in Treg was higher in multibacillary patients than in the contacts. Interestingly, there was a positive correlation of the bacillary index and number of lesions with the frequency of all Treg evaluated in patients. Conclusions/Significance: We have demonstrated for the first time that multibacillary leprosy patients under 15 years old have greater CD4+ and CD8+ Treg frequencies and these correlate with clinical and laboratorial aspects of disease. These findings suggest the involvement of these cells in the perpetuation of M. leprae infection. |
id |
UFC-7_168f698250c5c7b94b6c8de5606ba11f |
---|---|
oai_identifier_str |
oai:repositorio.ufc.br:riufc/8537 |
network_acronym_str |
UFC-7 |
network_name_str |
Repositório Institucional da Universidade Federal do Ceará (UFC) |
repository_id_str |
|
spelling |
Increased frequency of CD4 and CD8 regulatory T cells in individuals under 15 years with multibacillary leprosyHanseníase MultibacilarMycobacterium lepraeBackground: Leprosy is a chronic disease, caused by Mycobacterium leprae, which poses a serious public health problem worldwide. Its high incidence in people under 15 years old in Ceara´ state, Brazil, reflects the difficulty of its control. The spectrum of clinical manifestations is associated with the immune response developed, with the Th1 and Th2 responses being related to the paucibacillary and multibacillary forms, respectively. Regulatory T cells (Treg), which can suppress Th1 and Th2 response, have received special attention in the literature and have been associated with development of chronic infections. However, their role in leprosy in individuals under 15 years old has not yet been elucidated. We evaluated the frequency of CD4+/CD8+CD25highFOXP3+ and CD4+/CD8+CD25highFOXP3high cells in leprosy patients and household contacts, in both cases under 15 years old. Methodology/Principal Findings: PBMC from 12 patients and 17 contacts were cultured for 72 hours with anti-CD3 and anti-CD28 (activators) or with activators associated with total sonicated fraction of M. leprae. After culture, the frequency of CD4+/CD8+ Treg was identified by flow cytometry. Cells stimulated by activators and antigen from multibacillary patients showed Treg frequencies almost two times that of the contacts: CD4+FOXP3+ (21.9368.43 vs. 13.7968.19%, p = 0.0500), CD4+FOXP3high (10.3365.69 vs. 5.5764.03%, p = 0.0362), CD8+FOXP3+ (13.8869.19 vs. 6.1865.56%, p = 0.0230) and CD8+FOXP3high (5.3664.17 vs. 2.2362.68%, p = 0.0461). Furthermore, the mean fluorescence intensity of FOXP3 in Treg was higher in multibacillary patients than in the contacts. Interestingly, there was a positive correlation of the bacillary index and number of lesions with the frequency of all Treg evaluated in patients. Conclusions/Significance: We have demonstrated for the first time that multibacillary leprosy patients under 15 years old have greater CD4+ and CD8+ Treg frequencies and these correlate with clinical and laboratorial aspects of disease. These findings suggest the involvement of these cells in the perpetuation of M. leprae infection.Plos One2014-07-28T11:46:58Z2014-07-28T11:46:58Z2013-11info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfFERNANDES, C. et al. Increased frequency of CD4 and CD8 regulatory T cells in individuals under 15 years with multibacillary leprosy. Plos One, v. 8, n. 11, p. 1-9, nov. 2013.http://www.repositorio.ufc.br/handle/riufc/8537Fernandes, CamilaGonçalves, Heitor SáCabral, Paula Brito ePinto, Helena CâmaraPinto, Maria Isabel MoraesCâmara, Lilia Maria Carneiroengreponame:Repositório Institucional da Universidade Federal do Ceará (UFC)instname:Universidade Federal do Ceará (UFC)instacron:UFCinfo:eu-repo/semantics/openAccess2022-03-04T11:52:41Zoai:repositorio.ufc.br:riufc/8537Repositório InstitucionalPUBhttp://www.repositorio.ufc.br/ri-oai/requestbu@ufc.br || repositorio@ufc.bropendoar:2024-09-11T18:17:53.008838Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)false |
dc.title.none.fl_str_mv |
Increased frequency of CD4 and CD8 regulatory T cells in individuals under 15 years with multibacillary leprosy |
title |
Increased frequency of CD4 and CD8 regulatory T cells in individuals under 15 years with multibacillary leprosy |
spellingShingle |
Increased frequency of CD4 and CD8 regulatory T cells in individuals under 15 years with multibacillary leprosy Fernandes, Camila Hanseníase Multibacilar Mycobacterium leprae |
title_short |
Increased frequency of CD4 and CD8 regulatory T cells in individuals under 15 years with multibacillary leprosy |
title_full |
Increased frequency of CD4 and CD8 regulatory T cells in individuals under 15 years with multibacillary leprosy |
title_fullStr |
Increased frequency of CD4 and CD8 regulatory T cells in individuals under 15 years with multibacillary leprosy |
title_full_unstemmed |
Increased frequency of CD4 and CD8 regulatory T cells in individuals under 15 years with multibacillary leprosy |
title_sort |
Increased frequency of CD4 and CD8 regulatory T cells in individuals under 15 years with multibacillary leprosy |
author |
Fernandes, Camila |
author_facet |
Fernandes, Camila Gonçalves, Heitor Sá Cabral, Paula Brito e Pinto, Helena Câmara Pinto, Maria Isabel Moraes Câmara, Lilia Maria Carneiro |
author_role |
author |
author2 |
Gonçalves, Heitor Sá Cabral, Paula Brito e Pinto, Helena Câmara Pinto, Maria Isabel Moraes Câmara, Lilia Maria Carneiro |
author2_role |
author author author author author |
dc.contributor.author.fl_str_mv |
Fernandes, Camila Gonçalves, Heitor Sá Cabral, Paula Brito e Pinto, Helena Câmara Pinto, Maria Isabel Moraes Câmara, Lilia Maria Carneiro |
dc.subject.por.fl_str_mv |
Hanseníase Multibacilar Mycobacterium leprae |
topic |
Hanseníase Multibacilar Mycobacterium leprae |
description |
Background: Leprosy is a chronic disease, caused by Mycobacterium leprae, which poses a serious public health problem worldwide. Its high incidence in people under 15 years old in Ceara´ state, Brazil, reflects the difficulty of its control. The spectrum of clinical manifestations is associated with the immune response developed, with the Th1 and Th2 responses being related to the paucibacillary and multibacillary forms, respectively. Regulatory T cells (Treg), which can suppress Th1 and Th2 response, have received special attention in the literature and have been associated with development of chronic infections. However, their role in leprosy in individuals under 15 years old has not yet been elucidated. We evaluated the frequency of CD4+/CD8+CD25highFOXP3+ and CD4+/CD8+CD25highFOXP3high cells in leprosy patients and household contacts, in both cases under 15 years old. Methodology/Principal Findings: PBMC from 12 patients and 17 contacts were cultured for 72 hours with anti-CD3 and anti-CD28 (activators) or with activators associated with total sonicated fraction of M. leprae. After culture, the frequency of CD4+/CD8+ Treg was identified by flow cytometry. Cells stimulated by activators and antigen from multibacillary patients showed Treg frequencies almost two times that of the contacts: CD4+FOXP3+ (21.9368.43 vs. 13.7968.19%, p = 0.0500), CD4+FOXP3high (10.3365.69 vs. 5.5764.03%, p = 0.0362), CD8+FOXP3+ (13.8869.19 vs. 6.1865.56%, p = 0.0230) and CD8+FOXP3high (5.3664.17 vs. 2.2362.68%, p = 0.0461). Furthermore, the mean fluorescence intensity of FOXP3 in Treg was higher in multibacillary patients than in the contacts. Interestingly, there was a positive correlation of the bacillary index and number of lesions with the frequency of all Treg evaluated in patients. Conclusions/Significance: We have demonstrated for the first time that multibacillary leprosy patients under 15 years old have greater CD4+ and CD8+ Treg frequencies and these correlate with clinical and laboratorial aspects of disease. These findings suggest the involvement of these cells in the perpetuation of M. leprae infection. |
publishDate |
2013 |
dc.date.none.fl_str_mv |
2013-11 2014-07-28T11:46:58Z 2014-07-28T11:46:58Z |
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 |
FERNANDES, C. et al. Increased frequency of CD4 and CD8 regulatory T cells in individuals under 15 years with multibacillary leprosy. Plos One, v. 8, n. 11, p. 1-9, nov. 2013. http://www.repositorio.ufc.br/handle/riufc/8537 |
identifier_str_mv |
FERNANDES, C. et al. Increased frequency of CD4 and CD8 regulatory T cells in individuals under 15 years with multibacillary leprosy. Plos One, v. 8, n. 11, p. 1-9, nov. 2013. |
url |
http://www.repositorio.ufc.br/handle/riufc/8537 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Plos One |
publisher.none.fl_str_mv |
Plos One |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da Universidade Federal do Ceará (UFC) instname:Universidade Federal do Ceará (UFC) instacron:UFC |
instname_str |
Universidade Federal do Ceará (UFC) |
instacron_str |
UFC |
institution |
UFC |
reponame_str |
Repositório Institucional da Universidade Federal do Ceará (UFC) |
collection |
Repositório Institucional da Universidade Federal do Ceará (UFC) |
repository.name.fl_str_mv |
Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC) |
repository.mail.fl_str_mv |
bu@ufc.br || repositorio@ufc.br |
_version_ |
1813028743518617600 |