Impaired thymic output can be related to the low immune reconstitution and T cell repertoire disturbances in relapsing visceral leishmaniasis associated HIV/AIDS patients
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Outros Autores: | , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFMG |
Texto Completo: | https://doi.org/10.3389/fimmu.2020.00953 http://hdl.handle.net/1843/52092 https://orcid.org/0000-0001-5719-2945 https://orcid.org/0000-0002-3352-616X https://orcid.org/0000-0003-0538-7403 https://orcid.org/0000-0001-9341-5691 https://orcid.org/0000-0002-2193-2224 https://orcid.org/0000-0001-7455-2447 |
Resumo: | 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. |
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2023-04-17T21:48:12Z2023-04-17T21:48:12Z2020-05-2011https://doi.org/10.3389/fimmu.2020.009531664-3224http://hdl.handle.net/1843/52092https://orcid.org/0000-0001-5719-2945https://orcid.org/0000-0002-3352-616Xhttps://orcid.org/0000-0003-0538-7403https://orcid.org/0000-0001-9341-5691https://orcid.org/0000-0002-2193-2224https://orcid.org/0000-0001-7455-2447Background: 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.Introdução: Leishmaniose visceral/coinfectados pelo HIV (LV/LV) representam cerca de 8% dos casos notificados de LV no Brasil. As recidivas da infecção por Leishmania após tratamento antileishmania constituem um grande desafio na prática clínica devido à gravidade da doença e à resistência aos medicamentos. Mostramos que a LV/HIV (NR-) não recidivante evoluiu com aumento da contagem de células T CD4+ e redução das células T CD4+ e CD8+ ativadas após tratamento antileishmania. Este perfil imunológico não foi observado em pacientes com LV/HIV recidivante (R-), indicando um grau de comprometimento imunológico mais grave. O estado de ativação elevado pode estar relacionado a uma reconstituição imunológica deficiente e pode ajudar a explicar as frequentes recidivas na co-infecção LV/HIV. Nosso objetivo foi avaliar se esse ganho de células T estaria relacionado a alterações no repertório periférico de TCRVβ e estado inflamatório, bem como o possível envolvimento do timo na reposição desses linfócitos T neoformados. Métodos: Pacientes com LV/HIV, agrupados em não recidivantes (NR- = 6) e recidivantes (R- = 12), foram avaliados desde a fase ativa até 12 meses pós-tratamento (mpt). Pacientes infectados pelo HIV (não-LV) e indivíduos saudáveis (HS) foram incluídos. O repertório TCRVβ foi avaliado ex vivo por citometria de fluxo, enquanto os níveis plasmáticos de citocinas foram avaliados pelo ensaio Luminex. Para avaliar a produção tímica, o DNA foi extraído de PBMCs para quantificação dos círculos de excisão de rearranjo TCR (TREC) por qPCR. Resultados: Os casos de LV/HIV apresentaram perfil de mobilização alterado (expansões ou retrações) das famílias TCRVβ quando comparadas às HS independente da fase de seguimento (p < 0,05). O repertório de TCRVβ nas células T CD4+ foi mais homogêneo nos casos NR-VL/HIV, mas heterogêneo nas células T CD8+, uma vez que diferentes famílias Vβ foram mobilizadas. NR-VL/HIV teve o padrão inflamatório reduzido após 6 mpt. É importante ressaltar que os pacientes com LV/HIV apresentaram número de cópias TREC menor que os controles durante todo o acompanhamento. Um aumento de emigrantes tímicos recentes foi observado em indivíduos NR-VL/HIV em 10 mpt em comparação com pacientes R- (p < 0,01), que mantiveram conteúdos TREC mais baixos do que os controles HIV. Conclusões: Pacientes com LV/HIV que mantêm a função tímica, gerando novas células T, parecem capazes de repor o compartimento de linfócitos T com células efetoras, possibilitando o controle do parasita.CNPq - Conselho Nacional de Desenvolvimento Científico e TecnológicoFAPERJ - Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de JaneiroOutra AgênciaengUniversidade Federal de Minas GeraisUFMGBrasilHCL - HOSPITAL DAS CLINICASFrontiers in ImmunologyLeishmaniose visceralInfecções por HIVTimoLinfócitos TRecidivaImunidadeVisceral leishmaniasis/HIV-1 co-infectionThymic outputTCRVβ repertoireRelapsesImmune responseImpaired thymic output can be related to the low immune reconstitution and T cell repertoire disturbances in relapsing visceral leishmaniasis associated HIV/AIDS patientsA produção tímica prejudicada pode estar relacionada à baixa reconstituição imune e distúrbios do repertório de células T em pacientes com HIV/AIDS associados à leishmaniose visceral recidivanteinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttps://www.frontiersin.org/articles/10.3389/fimmu.2020.00953/fullMaria Luciana Silva FreitasGabriela Corrêa CastroGláucia Fernandes CotaCarmem Giacoia GrippAna Lúcia Teles RabelloJuliana Teixeira DutraZilton Farias Meira de VasconcelosWilson SavinoAlda Maria Da-CruzJoanna Reis Santos de Oliveiraapplication/pdfinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFMGinstname:Universidade Federal de Minas Gerais (UFMG)instacron:UFMGLICENSELicense.txtLicense.txttext/plain; charset=utf-82042https://repositorio.ufmg.br/bitstream/1843/52092/1/License.txtfa505098d172de0bc8864fc1287ffe22MD51ORIGINALImpaired Thymic Output Can Be Related to the Low Immune Reconstitution and T Cell Repertoire Disturbances in Relapsing Visceral Leishmaniasis Associated HIVAIDS Patients.pdfImpaired Thymic Output Can Be Related to the Low Immune Reconstitution and T Cell Repertoire Disturbances in Relapsing Visceral Leishmaniasis Associated HIVAIDS Patients.pdfapplication/pdf1282363https://repositorio.ufmg.br/bitstream/1843/52092/2/Impaired%20Thymic%20Output%20Can%20Be%20Related%20to%20the%20Low%20Immune%20Reconstitution%20and%20T%20Cell%20Repertoire%20Disturbances%20in%20Relapsing%20Visceral%20Leishmaniasis%20Associated%20HIVAIDS%20Patients.pdf277984f57f7302ed3c3e8b30638ab113MD521843/520922023-04-17 18:48:12.343oai:repositorio.ufmg.br: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Repositório de PublicaçõesPUBhttps://repositorio.ufmg.br/oaiopendoar:2023-04-17T21:48:12Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG)false |
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 |
dc.title.alternative.pt_BR.fl_str_mv |
A produção tímica prejudicada pode estar relacionada à baixa reconstituição imune e distúrbios do repertório de células T em pacientes com HIV/AIDS associados à leishmaniose visceral recidivante |
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 Maria Luciana Silva Freitas Visceral leishmaniasis/HIV-1 co-infection Thymic output TCRVβ repertoire Relapses Immune response Leishmaniose visceral Infecções por HIV Timo Linfócitos T Recidiva Imunidade |
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 |
Maria Luciana Silva Freitas |
author_facet |
Maria Luciana Silva Freitas Gabriela Corrêa Castro Gláucia Fernandes Cota Carmem Giacoia Gripp Ana Lúcia Teles Rabello Juliana Teixeira Dutra Zilton Farias Meira de Vasconcelos Wilson Savino Alda Maria Da-Cruz Joanna Reis Santos de Oliveira |
author_role |
author |
author2 |
Gabriela Corrêa Castro Gláucia Fernandes Cota Carmem Giacoia Gripp Ana Lúcia Teles Rabello Juliana Teixeira Dutra Zilton Farias Meira de Vasconcelos Wilson Savino Alda Maria Da-Cruz Joanna Reis Santos de Oliveira |
author2_role |
author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Maria Luciana Silva Freitas Gabriela Corrêa Castro Gláucia Fernandes Cota Carmem Giacoia Gripp Ana Lúcia Teles Rabello Juliana Teixeira Dutra Zilton Farias Meira de Vasconcelos Wilson Savino Alda Maria Da-Cruz Joanna Reis Santos de Oliveira |
dc.subject.por.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 Leishmaniose visceral Infecções por HIV Timo Linfócitos T Recidiva Imunidade |
dc.subject.other.pt_BR.fl_str_mv |
Leishmaniose visceral Infecções por HIV Timo Linfócitos T Recidiva Imunidade |
description |
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. |
publishDate |
2020 |
dc.date.issued.fl_str_mv |
2020-05-20 |
dc.date.accessioned.fl_str_mv |
2023-04-17T21:48:12Z |
dc.date.available.fl_str_mv |
2023-04-17T21:48:12Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/1843/52092 |
dc.identifier.doi.pt_BR.fl_str_mv |
https://doi.org/10.3389/fimmu.2020.00953 |
dc.identifier.issn.pt_BR.fl_str_mv |
1664-3224 |
dc.identifier.orcid.pt_BR.fl_str_mv |
https://orcid.org/0000-0001-5719-2945 https://orcid.org/0000-0002-3352-616X https://orcid.org/0000-0003-0538-7403 https://orcid.org/0000-0001-9341-5691 https://orcid.org/0000-0002-2193-2224 https://orcid.org/0000-0001-7455-2447 |
url |
https://doi.org/10.3389/fimmu.2020.00953 http://hdl.handle.net/1843/52092 https://orcid.org/0000-0001-5719-2945 https://orcid.org/0000-0002-3352-616X https://orcid.org/0000-0003-0538-7403 https://orcid.org/0000-0001-9341-5691 https://orcid.org/0000-0002-2193-2224 https://orcid.org/0000-0001-7455-2447 |
identifier_str_mv |
1664-3224 |
dc.language.iso.fl_str_mv |
eng |
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eng |
dc.relation.ispartof.pt_BR.fl_str_mv |
Frontiers in Immunology |
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info:eu-repo/semantics/openAccess |
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openAccess |
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Universidade Federal de Minas Gerais |
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UFMG |
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Brasil |
dc.publisher.department.fl_str_mv |
HCL - HOSPITAL DAS CLINICAS |
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Universidade Federal de Minas Gerais |
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