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

التفاصيل البيبلوغرافية
العنوان: Maturation and phenotypic heterogeneity of human CD4+ regulatory T cells from birth to adulthood and after allogeneic stem cell transplantation
المؤلفون: Tiago R. Matos, Masahiro Hirakawa, Ana C. Alho, Lars Neleman, Luis Graca, Jerome Ritz
المساهمون: Repositório da Universidade de Lisboa, Dermatology, Amsterdam institute for Infection and Immunity, AII - Infectious diseases
المصدر: Repositório Científico de Acesso Aberto de Portugal
Repositório Científico de Acesso Aberto de Portugal (RCAAP)
instacron:RCAAP
Frontiers in Immunology, Vol 11 (2021)
Frontiers in immunology, 11:570550. Frontiers Media S.A.
Frontiers in Immunology
بيانات النشر: Frontiers, 2020.
سنة النشر: 2020
مصطلحات موضوعية: Adult, Male, lcsh:Immunologic diseases. Allergy, medicine.medical_treatment, T cell, Immunology, Graft vs Host Disease, chemical and pharmacologic phenomena, ComputingMilieux_LEGALASPECTSOFCOMPUTING, Hematopoietic stem cell transplantation, Biology, T-Lymphocytes, Regulatory, Umbilical cord, Young Adult, medicine, Humans, Transplantation, Homologous, Immunology and Allergy, Mass cytometry, Cells, Cultured, Treg - regulatory T cell, alloHSCT, Original Research, Aged, GvHD, Diversity, Genetic heterogeneity, Hematopoietic Stem Cell Transplantation, hemic and immune systems, Middle Aged, CD4, Transplantation, Phenotype, medicine.anatomical_structure, Cord blood, CD4 Antigens, Female, Single-Cell Analysis, Stem cell, Heterogeneity, lcsh:RC581-607
الوصف: 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.
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/98980/2013
وصف الملف: application/pdf
اللغة: English
تدمد: 1664-3224
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::10d212f804dc42cd29f1bc575164c855
حقوق: OPEN
رقم الأكسشن: edsair.doi.dedup.....10d212f804dc42cd29f1bc575164c855
قاعدة البيانات: OpenAIRE