Impaired Thymic Output Can Be Related to the Low Immune Reconstitution and T Cell Repertoire Disturbances in Relapsing Visceral Leishmaniasis Associated HIV/AIDS Patients

Detalhes bibliográficos
Autor(a) principal: Silva-Freitas, Maria Luciana
Data de Publicação: 2020
Outros Autores: Corrêa-Castro, Gabriela, Cota, Glaucia Fernandes, Giacoia-Gripp, Carmem, Rabello, Ana Lucia Teles, Dutra, Juliana Teixeira, Vasconcelos, Zilton Farias Meira de, Savino, Wilson, Da-Cruz, Alda Maria, Santos-Oliveira, Joanna Reis
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/41918
Resumo: Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório Interdisciplinar de Pesquisas Médicas. Rio de Janeiro, RJ, Brasil.
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spelling Silva-Freitas, Maria LucianaCorrêa-Castro, GabrielaCota, Glaucia FernandesGiacoia-Gripp, CarmemRabello, Ana Lucia TelesDutra, Juliana TeixeiraVasconcelos, Zilton Farias Meira deSavino, WilsonDa-Cruz, Alda MariaSantos-Oliveira, Joanna Reis2020-06-26T19:05:11Z2020-06-26T19:05:11Z2020SILVA-FREITAS, Maria Luciana et al. Impaired Thymic Output Can Be Related to the Low Immune Reconstitution and T Cell Repertoire Disturbances in Relapsing Visceral Leishmaniasis Associated HIV/AIDS Patients. Frontiers in Immunology, v. 11, p. 1-14, 2020.1664-3224https://www.arca.fiocruz.br/handle/icict/4191810.3389/fimmu.2020.00953engFrontiers Research FoundationImpaired Thymic Output Can Be Related to the Low Immune Reconstitution and T Cell Repertoire Disturbances in Relapsing Visceral Leishmaniasis Associated HIV/AIDS Patientsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório Interdisciplinar de Pesquisas Médicas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório Interdisciplinar de Pesquisas Médicas. Rio de Janeiro, RJ, Brasil /Instituto Federal de Educação, Ciência e Tecnologia do Rio de Janeiro. Núcleo de Ciências Biomédicas Aplicadas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto René Rachou. Centro de Referência em Leishmanioses. Belo Horizonte, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de AIDS e Imunologia Molecular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto René Rachou. Centro de Referência em Leishmanioses. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira. Laboratório de Alta Complexidade. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira. Laboratório de Alta Complexidade. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa do Timo. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Instituto Nacional de Ciência e Tecnologia em Neuroimunomodulação. Rio de Janeiro, RJ, Brasil / Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro. Rede de Pesquisas em Saúde do Estado do Rio de Janeiro. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório Interdisciplinar de Pesquisas Médicas. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Instituto Nacional de Ciência e Tecnologia em Neuroimunomodulação. Rio de Janeiro, RJ, Brasil/Rede de Pesquisas em Saúde do Estado do Rio de Janeiro / FAPERJ, Rio de Janeiro, RJ, Brazil / Universidade do Estado do Rio de Janeiro. Faculdade de Ciências Médicas. Disciplina de Parasitologia. Rio de Janeiro,RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório Interdisciplinar de Pesquisas Médicas. Rio de Janeiro, RJ, Brasil / Instituto Federal de Educação, Ciência e Tecnologia do Rio de Janeiro. Núcleo de Ciências Biomédicas Aplicadas. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Instituto Nacional de Ciência e Tecnologia em Neuroimunomodulação. Rio de Janeiro, RJ, Brasil.Background: Visceral leishmaniasis/HIV-co-infected patients (VL/HIV) accounts for around 8% of VL reported cases in Brazil. Relapses of Leishmania infection after anti-leishmanial treatment constitute a great challenge in the clinical practice because of the disease severity and drug resistance. We have shown that non-relapsing-VL/HIV (NR-) evolved with increase of CD4+ T-cell counts and reduction of activated CD4+ and CD8+ T cells after anti-leishmanial treatment. This immune profile was not observed in relapsing-VL/HIV patients (R-), indicating a more severe immunological compromising degree. Elevated activation status may be related to a deficient immune reconstitution and could help to explain the frequent relapses in VL/HIV co-infection. Our aim was to evaluate if this gain of T cells was related to changes in the peripheral TCRVβ repertoire and inflammatory status, as well as the possible thymus involvement in the replenishment of these newly formed T lymphocytes. Methods: VL/HIV patients, grouped into non-relapsing (NR- = 6) and relapsing (R- = 12) were evaluated from the active phase up to 12 months post-treatment (mpt). HIV-infected patients (non-VL) and healthy subjects (HS) were included. The TCRVβ repertoire was evaluated ex vivo by flow cytometry, whereas the plasmatic cytokine levels were assessed by Luminex assay. To evaluate the thymic output, DNA was extracted from PBMCs for TCR rearrangement excision circles (TREC) quantification by qPCR. Results: VL/HIV cases presented an altered mobilization profile (expansions or retractions) of the TCRVβ families when compared to HS independent of the follow-up phase (p < 0.05). TCRVβ repertoire on CD4+ T-cells was more homogeneous in the NR-VL/HIV cases, but heterogeneous on CD8+ T-cells, since different Vβ-families were mobilized. NR-VL/HIV had the inflammatory pattern reduced after 6 mpt. Importantly, VL/HIV patients showed number of TREC copies lower than controls during all follow-up. An increase of recent thymic emigrants was observed in NR-VL/HIV individuals at 10 mpt compared to R- patients (p < 0.01), who maintained lower TREC contents than the HIV controls. Conclusions: VL/HIV patients that maintain the thymic function, thus generating new T-cells, seem able to replenish the T lymphocyte compartment with effector cells, then enabling parasite control.Visceral leishmaniasis/HIV-1 co-infectionThymic outputTCRVβ repertoireRelapsesImmune responseinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-83082https://www.arca.fiocruz.br/bitstream/icict/41918/1/license.txt9193a7c197bc67acd023525e72a03240MD51ORIGINALImpaired Thymic Output Can Be Related to the Low Immune Reconstitution and T Cell Repertoire Disturbances in Relapsing Visceral Leishmaniasis Associated HIV_AIDS Patients.pdfImpaired Thymic Output Can Be Related to the Low Immune Reconstitution and T Cell Repertoire Disturbances in Relapsing Visceral Leishmaniasis Associated HIV_AIDS Patients.pdfapplication/pdf1231904https://www.arca.fiocruz.br/bitstream/icict/41918/2/Impaired%20Thymic%20Output%20Can%20Be%20Related%20to%20the%20Low%20Immune%20Reconstitution%20and%20T%20Cell%20Repertoire%20Disturbances%20in%20Relapsing%20Visceral%20Leishmaniasis%20Associated%20HIV_AIDS%20Patients.pdf72b17f8827a88aa3c42e13a3c100a719MD52TEXTImpaired Thymic Output Can Be Related to the Low Immune Reconstitution and T Cell Repertoire Disturbances in Relapsing Visceral Leishmaniasis Associated HIV_AIDS Patients.pdf.txtImpaired Thymic Output Can Be Related to the Low Immune Reconstitution and T Cell Repertoire Disturbances in Relapsing Visceral Leishmaniasis Associated HIV_AIDS Patients.pdf.txtExtracted 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dc.title.pt_BR.fl_str_mv Impaired Thymic Output Can Be Related to the Low Immune Reconstitution and T Cell Repertoire Disturbances in Relapsing Visceral Leishmaniasis Associated HIV/AIDS Patients
title Impaired Thymic Output Can Be Related to the Low Immune Reconstitution and T Cell Repertoire Disturbances in Relapsing Visceral Leishmaniasis Associated HIV/AIDS Patients
spellingShingle Impaired Thymic Output Can Be Related to the Low Immune Reconstitution and T Cell Repertoire Disturbances in Relapsing Visceral Leishmaniasis Associated HIV/AIDS Patients
Silva-Freitas, Maria Luciana
Visceral leishmaniasis/HIV-1 co-infection
Thymic output
TCRVβ repertoire
Relapses
Immune response
title_short Impaired Thymic Output Can Be Related to the Low Immune Reconstitution and T Cell Repertoire Disturbances in Relapsing Visceral Leishmaniasis Associated HIV/AIDS Patients
title_full Impaired Thymic Output Can Be Related to the Low Immune Reconstitution and T Cell Repertoire Disturbances in Relapsing Visceral Leishmaniasis Associated HIV/AIDS Patients
title_fullStr Impaired Thymic Output Can Be Related to the Low Immune Reconstitution and T Cell Repertoire Disturbances in Relapsing Visceral Leishmaniasis Associated HIV/AIDS Patients
title_full_unstemmed Impaired Thymic Output Can Be Related to the Low Immune Reconstitution and T Cell Repertoire Disturbances in Relapsing Visceral Leishmaniasis Associated HIV/AIDS Patients
title_sort Impaired Thymic Output Can Be Related to the Low Immune Reconstitution and T Cell Repertoire Disturbances in Relapsing Visceral Leishmaniasis Associated HIV/AIDS Patients
author Silva-Freitas, Maria Luciana
author_facet Silva-Freitas, Maria Luciana
Corrêa-Castro, Gabriela
Cota, Glaucia Fernandes
Giacoia-Gripp, Carmem
Rabello, Ana Lucia Teles
Dutra, Juliana Teixeira
Vasconcelos, Zilton Farias Meira de
Savino, Wilson
Da-Cruz, Alda Maria
Santos-Oliveira, Joanna Reis
author_role author
author2 Corrêa-Castro, Gabriela
Cota, Glaucia Fernandes
Giacoia-Gripp, Carmem
Rabello, Ana Lucia Teles
Dutra, Juliana Teixeira
Vasconcelos, Zilton Farias Meira de
Savino, Wilson
Da-Cruz, Alda Maria
Santos-Oliveira, Joanna Reis
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Silva-Freitas, Maria Luciana
Corrêa-Castro, Gabriela
Cota, Glaucia Fernandes
Giacoia-Gripp, Carmem
Rabello, Ana Lucia Teles
Dutra, Juliana Teixeira
Vasconcelos, Zilton Farias Meira de
Savino, Wilson
Da-Cruz, Alda Maria
Santos-Oliveira, Joanna Reis
dc.subject.en.pt_BR.fl_str_mv Visceral leishmaniasis/HIV-1 co-infection
Thymic output
TCRVβ repertoire
Relapses
Immune response
topic Visceral leishmaniasis/HIV-1 co-infection
Thymic output
TCRVβ repertoire
Relapses
Immune response
description Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório Interdisciplinar de Pesquisas Médicas. Rio de Janeiro, RJ, Brasil.
publishDate 2020
dc.date.accessioned.fl_str_mv 2020-06-26T19:05:11Z
dc.date.available.fl_str_mv 2020-06-26T19:05:11Z
dc.date.issued.fl_str_mv 2020
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.citation.fl_str_mv SILVA-FREITAS, Maria Luciana et al. Impaired Thymic Output Can Be Related to the Low Immune Reconstitution and T Cell Repertoire Disturbances in Relapsing Visceral Leishmaniasis Associated HIV/AIDS Patients. Frontiers in Immunology, v. 11, p. 1-14, 2020.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/41918
dc.identifier.issn.pt_BR.fl_str_mv 1664-3224
dc.identifier.doi.none.fl_str_mv 10.3389/fimmu.2020.00953
identifier_str_mv SILVA-FREITAS, Maria Luciana et al. Impaired Thymic Output Can Be Related to the Low Immune Reconstitution and T Cell Repertoire Disturbances in Relapsing Visceral Leishmaniasis Associated HIV/AIDS Patients. Frontiers in Immunology, v. 11, p. 1-14, 2020.
1664-3224
10.3389/fimmu.2020.00953
url https://www.arca.fiocruz.br/handle/icict/41918
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.publisher.none.fl_str_mv Frontiers Research Foundation
publisher.none.fl_str_mv Frontiers Research Foundation
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
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instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
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