Estudo do perfil imunológico de subpopulações de células T naive e de memória em pacientes convalescentes da covid-19
Autor(a) principal: | |
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Data de Publicação: | 2023 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Biblioteca Digital de Teses e Dissertações da UFPB |
Texto Completo: | https://repositorio.ufpb.br/jspui/handle/123456789/29552 |
Resumo: | COVID-19 is a severe acute respiratory infection caused by the SARS-CoV-2 virus capable of suffering from different clinical conditions ranging from asymptomatic to severe, in which the host's immune response is crucial for its establishment. Long-lived SARS-CoV-2- specific CD4+ and CD8+ memory T cells are essential for long-term immune protection against COVID-19 as they have an increased ability to restrict viral replication in a secondary infection. Thus, the present study aims to investigate immunomodulatory mechanisms mediated by CD4+ and CD8+ T lymphocyte subtypes in patients who recovered from mild and severe forms of COVID-19 before vaccination by flow cytometry. Thus, peripheral blood samples were obtained from recruited volunteers and distributed into control (CTL - n = 9), mild (n =9), and severe (n = 6) groups. Samples of PBMCs were obtained and incubated under 3 different conditions: unstimulated (medium), and stimulated with SARSCoV-2 peptides (Pool Spike CoV-2 and Pool CoV-2. CD4+ and CD8+ T cells were analyzed and classified for CCR7+ and CD45RA+ expression in naive CD4+/CD8+ T cells (TN), CD4+/CD8+ central memory T cells (TMC), CD4+/CD8+ effector memory T cells (TME), and CD4+/CD8+ effector memory T cells that reexpress CD45RA (TMERA). Thus, in the different subpopulations mentioned above, cytokines (IL-10, IFN-y, TNF-α, and IL-17) and activation markers (CD69, CD137, and Ki67) were expressed analyzed by flow cytometry. Pool Spthe ike CoV-2 and Pool CoV-2 stimulus elicited a higher frequency of CD8+ TCM cells and CD4+ TEMRA cells in recovered mild group. CD4+ and CD8+ TCM and TEM cells showed heterogeneity in CD137 and CD69 activation marker expressions between mild and severe recovered groups. Also, we observed a predominance in CD137 expression by naive CD4+ and CD8+ cells, TCM, and TEM from the mild recovered group when stimulated with antigenic pools. Additionality, a higher CD69 expression from the severe recovered group by CD4+ and CD8+ TEMRA cells was observed under SARS-CoV-2 Epitope Pools. CD4+ and CD8+ naïve, TCM and TEM cells subsets from recovered mild volunteers had higher expression of TNF-α while the expression partner of IFN-γ, IL-10, and IL-17 point to an antiviral signature by TEMRA CD8+ cells. Our findings contribute to the elucidation of the functional capabilities of each subpopulation of memory T cells during SARS CoV-2 antigenic reexposure, as well as their role in disease outcome in individuals recovered from COVID-19. |
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Estudo do perfil imunológico de subpopulações de células T naive e de memória em pacientes convalescentes da covid-19Pandemia - Covid-19Resposta imuneSubtipos de linfócitos TInfecção por sars-CoV-2Memória imunológicaImmunological memoryImmune responseT Lymphocytes subsetsSARS-CoV-2 infectionCOVID-19CNPQ::CIENCIAS BIOLOGICAS::FISIOLOGIACOVID-19 is a severe acute respiratory infection caused by the SARS-CoV-2 virus capable of suffering from different clinical conditions ranging from asymptomatic to severe, in which the host's immune response is crucial for its establishment. Long-lived SARS-CoV-2- specific CD4+ and CD8+ memory T cells are essential for long-term immune protection against COVID-19 as they have an increased ability to restrict viral replication in a secondary infection. Thus, the present study aims to investigate immunomodulatory mechanisms mediated by CD4+ and CD8+ T lymphocyte subtypes in patients who recovered from mild and severe forms of COVID-19 before vaccination by flow cytometry. Thus, peripheral blood samples were obtained from recruited volunteers and distributed into control (CTL - n = 9), mild (n =9), and severe (n = 6) groups. Samples of PBMCs were obtained and incubated under 3 different conditions: unstimulated (medium), and stimulated with SARSCoV-2 peptides (Pool Spike CoV-2 and Pool CoV-2. CD4+ and CD8+ T cells were analyzed and classified for CCR7+ and CD45RA+ expression in naive CD4+/CD8+ T cells (TN), CD4+/CD8+ central memory T cells (TMC), CD4+/CD8+ effector memory T cells (TME), and CD4+/CD8+ effector memory T cells that reexpress CD45RA (TMERA). Thus, in the different subpopulations mentioned above, cytokines (IL-10, IFN-y, TNF-α, and IL-17) and activation markers (CD69, CD137, and Ki67) were expressed analyzed by flow cytometry. Pool Spthe ike CoV-2 and Pool CoV-2 stimulus elicited a higher frequency of CD8+ TCM cells and CD4+ TEMRA cells in recovered mild group. CD4+ and CD8+ TCM and TEM cells showed heterogeneity in CD137 and CD69 activation marker expressions between mild and severe recovered groups. Also, we observed a predominance in CD137 expression by naive CD4+ and CD8+ cells, TCM, and TEM from the mild recovered group when stimulated with antigenic pools. Additionality, a higher CD69 expression from the severe recovered group by CD4+ and CD8+ TEMRA cells was observed under SARS-CoV-2 Epitope Pools. CD4+ and CD8+ naïve, TCM and TEM cells subsets from recovered mild volunteers had higher expression of TNF-α while the expression partner of IFN-γ, IL-10, and IL-17 point to an antiviral signature by TEMRA CD8+ cells. Our findings contribute to the elucidation of the functional capabilities of each subpopulation of memory T cells during SARS CoV-2 antigenic reexposure, as well as their role in disease outcome in individuals recovered from COVID-19.A COVID-19 é uma infecção respiratória aguda grave, causada pelo vírus SARS-CoV-2 capaz de desencadear diferentes quadros clínicos que variam de assintomático a grave, nos quais a resposta imune do hospedeiro é determinante para o seu estabelecimento. As células T de memória CD4+ e CD8+ específicas para SARS-CoV-2 de vida longa são essenciais para a proteção imunológica de longo prazo para a COVID-19, pois têm uma capacidade aumentada de restringir a replicação viral em uma infecção secundária. Nesse contexto, o presente estudo tem como objetivo investigar os mecanismos imunomoduladores mediados pelos subtipos de linfócitos T CD4+ e CD8+ em pacientes que se recuperaram de formas leve e grave de COVID-19. Para tal, amostras de sangue periférico foram coletadas de voluntários recrutados entre o período de novembro de 2020 a junho de 2021, antes de serem vacinados, e distribuídos nos grupos controle (CTL - n = 9), leve (n = 9) e grave (n = 6). Amostras de PBMCs foram obtidas e incubadas sob 3 diferentes condições: não estimuladas (meio), e estimuladas com peptídeos SARS-CoV-2 (Pool Spike CoV-2 e Pool CoV-2). As células T CD4+/CD8+ foram analisadas e classificadas quanto a expressão de CCR7+ e CD45RA+ em T CD4+/CD8+ naive (TN), células T CD4+/CD8+ de memória central (TMC), células T CD4+/CD8+ de memória efetora (TME) e células T CD4+/CD8+ de memória efetora que reexpressam CD45RA (TMERA). Assim, nas diferentes subpopulações mencionadas acima, a expressão de citocinas (IL-10, IFN-y, TNF-α e IL-17) e marcadores de ativação (CD69, CD137 e Ki67) foi analisada por citometria de fluxo. Os estímulos Pool Spike CoV-2 e Pool CoV-2 provocaram uma frequência mais alta de células CD8+ TCM e células CD4+ TEMRA no grupo leve recuperado. Células TCM e TEM CD4+ e CD8+ mostraram heterogeneidade na expressão de marcadores de ativação CD137 e CD69 entre grupos recuperados leves e graves. Além disso, observamos uma predominância na expressão de CD137 por células CD4+ e CD8+ virgens, TCM e TEM do grupo leve recuperado quando estimulado com pools antigênicos. Além disso, uma maior expressão de CD69 do grupo recuperado grave por células TEMRA CD4+ e CD8+ foi observada em pools de epítopos SARS-CoV-2. Os subconjuntos de células CD4+ e CD8+ virgens, TCM e TEM de voluntários leves recuperados apresentaram maior expressão de TNF-α, enquanto a expressão de IFN-γ, IL-10 e IL-17 aponta para uma assinatura antiviral por células TEMRA CD8+. Nossas descobertas contribuem para a elucidação acerca das capacidades funcionais de cada subpopulação de células T de memória durante a reexposição antigênica SARS CoV2, bem como sua atuação no desfecho da doença em indivíduos recuperados da COVID-19.Universidade Federal da ParaíbaBrasilCiências FisiológicasPrograma Multicêntrico de Pós-Graduação em Ciências FisiológicasUFPBLima, Tatjana Keesen de Souzahttp://lattes.cnpq.br/5504382837656473Peixoto, Rephany Fonseca2024-02-20T21:47:52Z2023-06-152024-02-20T21:47:52Z2023-04-04info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesishttps://repositorio.ufpb.br/jspui/handle/123456789/29552porAttribution-NoDerivs 3.0 Brazilhttp://creativecommons.org/licenses/by-nd/3.0/br/info:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da UFPBinstname:Universidade Federal da Paraíba (UFPB)instacron:UFPB2024-02-21T06:05:14Zoai:repositorio.ufpb.br:123456789/29552Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufpb.br/PUBhttp://tede.biblioteca.ufpb.br:8080/oai/requestdiretoria@ufpb.br|| diretoria@ufpb.bropendoar:2024-02-21T06:05:14Biblioteca Digital de Teses e Dissertações da UFPB - Universidade Federal da Paraíba (UFPB)false |
dc.title.none.fl_str_mv |
Estudo do perfil imunológico de subpopulações de células T naive e de memória em pacientes convalescentes da covid-19 |
title |
Estudo do perfil imunológico de subpopulações de células T naive e de memória em pacientes convalescentes da covid-19 |
spellingShingle |
Estudo do perfil imunológico de subpopulações de células T naive e de memória em pacientes convalescentes da covid-19 Peixoto, Rephany Fonseca Pandemia - Covid-19 Resposta imune Subtipos de linfócitos T Infecção por sars-CoV-2 Memória imunológica Immunological memory Immune response T Lymphocytes subsets SARS-CoV-2 infection COVID-19 CNPQ::CIENCIAS BIOLOGICAS::FISIOLOGIA |
title_short |
Estudo do perfil imunológico de subpopulações de células T naive e de memória em pacientes convalescentes da covid-19 |
title_full |
Estudo do perfil imunológico de subpopulações de células T naive e de memória em pacientes convalescentes da covid-19 |
title_fullStr |
Estudo do perfil imunológico de subpopulações de células T naive e de memória em pacientes convalescentes da covid-19 |
title_full_unstemmed |
Estudo do perfil imunológico de subpopulações de células T naive e de memória em pacientes convalescentes da covid-19 |
title_sort |
Estudo do perfil imunológico de subpopulações de células T naive e de memória em pacientes convalescentes da covid-19 |
author |
Peixoto, Rephany Fonseca |
author_facet |
Peixoto, Rephany Fonseca |
author_role |
author |
dc.contributor.none.fl_str_mv |
Lima, Tatjana Keesen de Souza http://lattes.cnpq.br/5504382837656473 |
dc.contributor.author.fl_str_mv |
Peixoto, Rephany Fonseca |
dc.subject.por.fl_str_mv |
Pandemia - Covid-19 Resposta imune Subtipos de linfócitos T Infecção por sars-CoV-2 Memória imunológica Immunological memory Immune response T Lymphocytes subsets SARS-CoV-2 infection COVID-19 CNPQ::CIENCIAS BIOLOGICAS::FISIOLOGIA |
topic |
Pandemia - Covid-19 Resposta imune Subtipos de linfócitos T Infecção por sars-CoV-2 Memória imunológica Immunological memory Immune response T Lymphocytes subsets SARS-CoV-2 infection COVID-19 CNPQ::CIENCIAS BIOLOGICAS::FISIOLOGIA |
description |
COVID-19 is a severe acute respiratory infection caused by the SARS-CoV-2 virus capable of suffering from different clinical conditions ranging from asymptomatic to severe, in which the host's immune response is crucial for its establishment. Long-lived SARS-CoV-2- specific CD4+ and CD8+ memory T cells are essential for long-term immune protection against COVID-19 as they have an increased ability to restrict viral replication in a secondary infection. Thus, the present study aims to investigate immunomodulatory mechanisms mediated by CD4+ and CD8+ T lymphocyte subtypes in patients who recovered from mild and severe forms of COVID-19 before vaccination by flow cytometry. Thus, peripheral blood samples were obtained from recruited volunteers and distributed into control (CTL - n = 9), mild (n =9), and severe (n = 6) groups. Samples of PBMCs were obtained and incubated under 3 different conditions: unstimulated (medium), and stimulated with SARSCoV-2 peptides (Pool Spike CoV-2 and Pool CoV-2. CD4+ and CD8+ T cells were analyzed and classified for CCR7+ and CD45RA+ expression in naive CD4+/CD8+ T cells (TN), CD4+/CD8+ central memory T cells (TMC), CD4+/CD8+ effector memory T cells (TME), and CD4+/CD8+ effector memory T cells that reexpress CD45RA (TMERA). Thus, in the different subpopulations mentioned above, cytokines (IL-10, IFN-y, TNF-α, and IL-17) and activation markers (CD69, CD137, and Ki67) were expressed analyzed by flow cytometry. Pool Spthe ike CoV-2 and Pool CoV-2 stimulus elicited a higher frequency of CD8+ TCM cells and CD4+ TEMRA cells in recovered mild group. CD4+ and CD8+ TCM and TEM cells showed heterogeneity in CD137 and CD69 activation marker expressions between mild and severe recovered groups. Also, we observed a predominance in CD137 expression by naive CD4+ and CD8+ cells, TCM, and TEM from the mild recovered group when stimulated with antigenic pools. Additionality, a higher CD69 expression from the severe recovered group by CD4+ and CD8+ TEMRA cells was observed under SARS-CoV-2 Epitope Pools. CD4+ and CD8+ naïve, TCM and TEM cells subsets from recovered mild volunteers had higher expression of TNF-α while the expression partner of IFN-γ, IL-10, and IL-17 point to an antiviral signature by TEMRA CD8+ cells. Our findings contribute to the elucidation of the functional capabilities of each subpopulation of memory T cells during SARS CoV-2 antigenic reexposure, as well as their role in disease outcome in individuals recovered from COVID-19. |
publishDate |
2023 |
dc.date.none.fl_str_mv |
2023-06-15 2023-04-04 2024-02-20T21:47:52Z 2024-02-20T21:47:52Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
format |
doctoralThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
https://repositorio.ufpb.br/jspui/handle/123456789/29552 |
url |
https://repositorio.ufpb.br/jspui/handle/123456789/29552 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.rights.driver.fl_str_mv |
Attribution-NoDerivs 3.0 Brazil http://creativecommons.org/licenses/by-nd/3.0/br/ info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
Attribution-NoDerivs 3.0 Brazil http://creativecommons.org/licenses/by-nd/3.0/br/ |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Universidade Federal da Paraíba Brasil Ciências Fisiológicas Programa Multicêntrico de Pós-Graduação em Ciências Fisiológicas UFPB |
publisher.none.fl_str_mv |
Universidade Federal da Paraíba Brasil Ciências Fisiológicas Programa Multicêntrico de Pós-Graduação em Ciências Fisiológicas UFPB |
dc.source.none.fl_str_mv |
reponame:Biblioteca Digital de Teses e Dissertações da UFPB instname:Universidade Federal da Paraíba (UFPB) instacron:UFPB |
instname_str |
Universidade Federal da Paraíba (UFPB) |
instacron_str |
UFPB |
institution |
UFPB |
reponame_str |
Biblioteca Digital de Teses e Dissertações da UFPB |
collection |
Biblioteca Digital de Teses e Dissertações da UFPB |
repository.name.fl_str_mv |
Biblioteca Digital de Teses e Dissertações da UFPB - Universidade Federal da Paraíba (UFPB) |
repository.mail.fl_str_mv |
diretoria@ufpb.br|| diretoria@ufpb.br |
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1801843015551025152 |