Follicular like T cells in monoclonal gammopathies
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Tipo de documento: | Dissertação |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10773/31126 |
Resumo: | Monoclonal gammopathies result from the proliferation of a single clone of plasma cells (PCs) and include disorders such as monoclonal gammopathy of undetermined significance (MGUS) and Multiple Myeloma (MM). It is speculated that the triggering event that turns healthy PCs into pathological PCs happens in the germinal centre (GC), most likely during a process known as somatic hypermutation (SHM), which takes place during antigen affinity maturation. GC maintenance, as well as, GC B-cell selection depends on T cell help, particularly on follicular T cells. In this study we aimed to analyse different T cell populations in the BM microenvironment of patients with monoclonal gammopathies, focusing on follicular-like T cells. Through multiparameter flow-cytometry we analysed CD4+, CD8+, γδ+, CD4-CD8- αβ+ and CD4+CD8+ T cells and identified follicular-like cells based on the expression of CXCR5, as well as activated T cells according to CD25 and HLA-DR expression, in all T cell subpopulations. We observed a general increase of follicular-like T cells in these patients, reaching statistical significance in the Th reg follicular-like cell subset when comparing the MM group with controls. The γδ+ follicular-like T subset was, however decreased in all MM groups. Interestingly, a decrease in activated follicular-like T cells was observed. In conclusion, despite of follicular-like T cells being increased in monoclonal gammopathy patients, they tend to less activated, which suggests that these cells are either not responding to the BM microenvironment or being negatively regulated. Our study population was small so further studies concerning follicular-like T cells in the BM of patients with monoclonal gammopathies may help understand the role of these cells in the BM microenvironment. |
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Follicular like T cells in monoclonal gammopathiesMonoclonal gammopathiesMonoclonal gammopathy of undetermined significanceMultiple myelomaFollicular-like T cellsMonoclonal gammopathies result from the proliferation of a single clone of plasma cells (PCs) and include disorders such as monoclonal gammopathy of undetermined significance (MGUS) and Multiple Myeloma (MM). It is speculated that the triggering event that turns healthy PCs into pathological PCs happens in the germinal centre (GC), most likely during a process known as somatic hypermutation (SHM), which takes place during antigen affinity maturation. GC maintenance, as well as, GC B-cell selection depends on T cell help, particularly on follicular T cells. In this study we aimed to analyse different T cell populations in the BM microenvironment of patients with monoclonal gammopathies, focusing on follicular-like T cells. Through multiparameter flow-cytometry we analysed CD4+, CD8+, γδ+, CD4-CD8- αβ+ and CD4+CD8+ T cells and identified follicular-like cells based on the expression of CXCR5, as well as activated T cells according to CD25 and HLA-DR expression, in all T cell subpopulations. We observed a general increase of follicular-like T cells in these patients, reaching statistical significance in the Th reg follicular-like cell subset when comparing the MM group with controls. The γδ+ follicular-like T subset was, however decreased in all MM groups. Interestingly, a decrease in activated follicular-like T cells was observed. In conclusion, despite of follicular-like T cells being increased in monoclonal gammopathy patients, they tend to less activated, which suggests that these cells are either not responding to the BM microenvironment or being negatively regulated. Our study population was small so further studies concerning follicular-like T cells in the BM of patients with monoclonal gammopathies may help understand the role of these cells in the BM microenvironment.As gamapatias monoclonais constituem um grupo de doenças, como a gamapatia monoclonal de significado indeterminado e o mieloma múltiplo (MM), que resultam da proliferação de células plasmáticas clonais. As células plasmáticas diferenciam-se a partir de linfócitos B que sobreviveram ao processo de maturação por afinidade no centro germinativo e que depois migraram para a medula óssea. Especula-se que o evento responsável pela transformação das células plasmáticas saudáveis em células patológicas ocorre no centro germinativo, provavelmente durante o processo de hipermutações somáticas. A manutenção dos centros germinativos, bem como a seleção de células B de elevada afinidade, depende das células T, especialmente do subtipo células T foliculares. Este estudo teve como objetivo a análise das diferentes populações de células T na medula óssea de doentes com gamapatias monoclonais, particularmente as células T foliculares. Recorrendo à técnica de citometria de fluxo, analisámos as subpopulações de células T CD4+, CD8+, γδ+, CD4-CD8- αβ+ e CD4+CD8+. As células com fenótipo folicular foram identificadas com base na expressão de CXCR5 e as células T ativadas de acordo com a expressão de CD25 ou HLA-DR. Os nossos resultados mostraram um aumento na frequência das células T com fenótipo folicular nestes doentes, obtendo significado estatístico no subconjunto das células T reguladoras com fenótipo folicular, quando comparados os grupos com MM e controlo. Contudo, a frequência de células T γδ+ com fenótipo folicular estava diminuída em todos os grupos com MM. Curiosamente, observou-se uma diminuição na frequência de células T com fenótipo folicular ativadas. Em suma, apesar de as células T com fenótipo folicular se apresentarem tendencialmente aumentadas em doentes com gamapatias monoclonais, estas parecem estar menos ativadas, o que sugere que estas células se encontram irresponsivas ao microambiente medular ou, por outro lado, estão a ser reguladas negativamente. Atendendo a que a nossa amostra de estudo era limitada, estudos adicionais são necessários para estabelecer o papel das células T foliculares na medula óssea e no microambiente tumoral de doentes com gamapatias monoclonais.2021-04-07T13:14:35Z2021-03-22T00:00:00Z2021-03-22info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/10773/31126engSilva, Ana Catarina Lopes einfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-02-22T11:59:59Zoai:ria.ua.pt:10773/31126Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:03:02.071922Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Follicular like T cells in monoclonal gammopathies |
title |
Follicular like T cells in monoclonal gammopathies |
spellingShingle |
Follicular like T cells in monoclonal gammopathies Silva, Ana Catarina Lopes e Monoclonal gammopathies Monoclonal gammopathy of undetermined significance Multiple myeloma Follicular-like T cells |
title_short |
Follicular like T cells in monoclonal gammopathies |
title_full |
Follicular like T cells in monoclonal gammopathies |
title_fullStr |
Follicular like T cells in monoclonal gammopathies |
title_full_unstemmed |
Follicular like T cells in monoclonal gammopathies |
title_sort |
Follicular like T cells in monoclonal gammopathies |
author |
Silva, Ana Catarina Lopes e |
author_facet |
Silva, Ana Catarina Lopes e |
author_role |
author |
dc.contributor.author.fl_str_mv |
Silva, Ana Catarina Lopes e |
dc.subject.por.fl_str_mv |
Monoclonal gammopathies Monoclonal gammopathy of undetermined significance Multiple myeloma Follicular-like T cells |
topic |
Monoclonal gammopathies Monoclonal gammopathy of undetermined significance Multiple myeloma Follicular-like T cells |
description |
Monoclonal gammopathies result from the proliferation of a single clone of plasma cells (PCs) and include disorders such as monoclonal gammopathy of undetermined significance (MGUS) and Multiple Myeloma (MM). It is speculated that the triggering event that turns healthy PCs into pathological PCs happens in the germinal centre (GC), most likely during a process known as somatic hypermutation (SHM), which takes place during antigen affinity maturation. GC maintenance, as well as, GC B-cell selection depends on T cell help, particularly on follicular T cells. In this study we aimed to analyse different T cell populations in the BM microenvironment of patients with monoclonal gammopathies, focusing on follicular-like T cells. Through multiparameter flow-cytometry we analysed CD4+, CD8+, γδ+, CD4-CD8- αβ+ and CD4+CD8+ T cells and identified follicular-like cells based on the expression of CXCR5, as well as activated T cells according to CD25 and HLA-DR expression, in all T cell subpopulations. We observed a general increase of follicular-like T cells in these patients, reaching statistical significance in the Th reg follicular-like cell subset when comparing the MM group with controls. The γδ+ follicular-like T subset was, however decreased in all MM groups. Interestingly, a decrease in activated follicular-like T cells was observed. In conclusion, despite of follicular-like T cells being increased in monoclonal gammopathy patients, they tend to less activated, which suggests that these cells are either not responding to the BM microenvironment or being negatively regulated. Our study population was small so further studies concerning follicular-like T cells in the BM of patients with monoclonal gammopathies may help understand the role of these cells in the BM microenvironment. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-04-07T13:14:35Z 2021-03-22T00:00:00Z 2021-03-22 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
format |
masterThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10773/31126 |
url |
http://hdl.handle.net/10773/31126 |
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.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799137685718171648 |