Maturation and phenotypic heterogeneity of human CD4+ regulatory T cells from birth to adulthood and after allogeneic stem cell transplantation

Detalhes bibliográficos
Autor(a) principal: Matos, Tiago R.
Data de Publicação: 2020
Outros Autores: Hirakawa, Masahiro, Alho, Ana Cristina, Neleman, Lars, Graca, Luis, Ritz, Jerome
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10451/46215
Resumo: Copyright © 2021 Matos, Hirakawa, Alho, Neleman, Graca and Ritz. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
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spelling Maturation and phenotypic heterogeneity of human CD4+ regulatory T cells from birth to adulthood and after allogeneic stem cell transplantationTreg - regulatory T cellImmunologyT cellHeterogeneityDiversityGvHDalloHSCTCD4Copyright © 2021 Matos, Hirakawa, Alho, Neleman, Graca and Ritz. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.CD4+ Regulatory T cells (Treg) play a critical role in maintaining immune homeostasis. Various Treg subsets have been identified, however the heterogeneity of Treg subpopulations during development remains uncharacterized. Using mass cytometry we obtained single cell data on expression of 35 functional markers to examine the heterogeneity of Treg cells at birth and in adults. Unsupervised clustering algorithms FlowSOM and ACCENSE were used to quantify Treg heterogeneity. As expected, Treg in umbilical cord blood were predominately naïve while Treg in adult blood were predominately central memory and effector memory cells. Although umbilical cord blood Treg are mostly naïve cells, we observed multiple phenotypic Treg subsets in cord blood. Nevertheless, peripheral blood in adults contained higher percentages of Treg and the heterogeneity of Treg was significantly increased in adults. We also studied Treg heterogeneity throughout a 2-year period after allogeneic hematopoietic stem cell transplantation (alloHSCT) and in patients with chronic graft-versus-host disease (cGVHD). Treg heterogeneity recovered rapidly after alloHSCT and gradually increased in the first two years post-transplant. However, patients with cGVHD had significantly fewer distinct Treg subpopulations, proposing a correlation between a disrupted Treg heterogeneity and cGVHD. Our study is the first to compare human Treg heterogeneity at birth, in healthy adults and in patients after alloHSCT with and without cGVHD. This approach to characterize Treg heterogeneity based on expression of a large panel of functional markers may enable future studies to identify specific Treg defects that contribute to immune dysfunction.This work was supported by NIH grant P01CA229092, EADV Research Fellowship, Rene-Touraine Fellowship and a generous contribution from the Fundação para a Ciência e a Tecnologia (FCT), FCT SFRH/BD/98980/2013FrontiersRepositório da Universidade de LisboaMatos, Tiago R.Hirakawa, MasahiroAlho, Ana CristinaNeleman, LarsGraca, LuisRitz, Jerome2021-02-05T18:50:30Z20202020-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/46215engFront Immunol. 2021 Jan 18;11:57055010.3389/fimmu.2020. 5705501664-3224info: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:RCAAP2023-11-08T16:48:26Zoai:repositorio.ul.pt:10451/46215Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:58:28.257157Repositório 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 Maturation and phenotypic heterogeneity of human CD4+ regulatory T cells from birth to adulthood and after allogeneic stem cell transplantation
title Maturation and phenotypic heterogeneity of human CD4+ regulatory T cells from birth to adulthood and after allogeneic stem cell transplantation
spellingShingle Maturation and phenotypic heterogeneity of human CD4+ regulatory T cells from birth to adulthood and after allogeneic stem cell transplantation
Matos, Tiago R.
Treg - regulatory T cell
Immunology
T cell
Heterogeneity
Diversity
GvHD
alloHSCT
CD4
title_short Maturation and phenotypic heterogeneity of human CD4+ regulatory T cells from birth to adulthood and after allogeneic stem cell transplantation
title_full Maturation and phenotypic heterogeneity of human CD4+ regulatory T cells from birth to adulthood and after allogeneic stem cell transplantation
title_fullStr Maturation and phenotypic heterogeneity of human CD4+ regulatory T cells from birth to adulthood and after allogeneic stem cell transplantation
title_full_unstemmed Maturation and phenotypic heterogeneity of human CD4+ regulatory T cells from birth to adulthood and after allogeneic stem cell transplantation
title_sort Maturation and phenotypic heterogeneity of human CD4+ regulatory T cells from birth to adulthood and after allogeneic stem cell transplantation
author Matos, Tiago R.
author_facet Matos, Tiago R.
Hirakawa, Masahiro
Alho, Ana Cristina
Neleman, Lars
Graca, Luis
Ritz, Jerome
author_role author
author2 Hirakawa, Masahiro
Alho, Ana Cristina
Neleman, Lars
Graca, Luis
Ritz, Jerome
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Matos, Tiago R.
Hirakawa, Masahiro
Alho, Ana Cristina
Neleman, Lars
Graca, Luis
Ritz, Jerome
dc.subject.por.fl_str_mv Treg - regulatory T cell
Immunology
T cell
Heterogeneity
Diversity
GvHD
alloHSCT
CD4
topic Treg - regulatory T cell
Immunology
T cell
Heterogeneity
Diversity
GvHD
alloHSCT
CD4
description Copyright © 2021 Matos, Hirakawa, Alho, Neleman, Graca and Ritz. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
publishDate 2020
dc.date.none.fl_str_mv 2020
2020-01-01T00:00:00Z
2021-02-05T18:50:30Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
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format article
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dc.identifier.uri.fl_str_mv http://hdl.handle.net/10451/46215
url http://hdl.handle.net/10451/46215
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Front Immunol. 2021 Jan 18;11:570550
10.3389/fimmu.2020. 570550
1664-3224
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