Maturation and Phenotypic Heterogeneity of Human CD4+ Regulatory T Cells From Birth to Adulthood and After Allogeneic Stem Cell Transplantation
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 functio...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2020.570550/full |
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| author | Tiago R. Matos Tiago R. Matos Tiago R. Matos Tiago R. Matos Masahiro Hirakawa Masahiro Hirakawa Ana C. Alho Ana C. Alho Ana C. Alho Lars Neleman Luis Graca Jerome Ritz Jerome Ritz |
| author_facet | Tiago R. Matos Tiago R. Matos Tiago R. Matos Tiago R. Matos Masahiro Hirakawa Masahiro Hirakawa Ana C. Alho Ana C. Alho Ana C. Alho Lars Neleman Luis Graca Jerome Ritz Jerome Ritz |
| author_sort | Tiago R. Matos |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-18T23:11:42Z |
| format | Article |
| id | doaj.art-caac1a382d9b422a9d093fb50848a79f |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-18T23:11:42Z |
| publishDate | 2021-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-caac1a382d9b422a9d093fb50848a79f2022-12-21T20:48:19ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-01-011110.3389/fimmu.2020.570550570550Maturation and Phenotypic Heterogeneity of Human CD4+ Regulatory T Cells From Birth to Adulthood and After Allogeneic Stem Cell TransplantationTiago R. Matos0Tiago R. Matos1Tiago R. Matos2Tiago R. Matos3Masahiro Hirakawa4Masahiro Hirakawa5Ana C. Alho6Ana C. Alho7Ana C. Alho8Lars Neleman9Luis Graca10Jerome Ritz11Jerome Ritz12Division of Hematologic Malignancies and Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, United StatesHarvard Medical School, Boston, MA, United StatesInstituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, PortugalAmsterdam University Medical Centers, Department of Dermatology, University of Amsterdam, Amsterdam, NetherlandsDivision of Hematologic Malignancies and Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, United StatesHarvard Medical School, Boston, MA, United StatesDivision of Hematologic Malignancies and Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, United StatesHarvard Medical School, Boston, MA, United StatesInstituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, PortugalAmsterdam University Medical Centers, Department of Dermatology, University of Amsterdam, Amsterdam, NetherlandsInstituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, PortugalDivision of Hematologic Malignancies and Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, United StatesHarvard Medical School, Boston, MA, United StatesCD4+ 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.https://www.frontiersin.org/articles/10.3389/fimmu.2020.570550/fullTreg - regulatory T cellimmunologyT cellheterogeneitydiversityGvHD |
| spellingShingle | Tiago R. Matos Tiago R. Matos Tiago R. Matos Tiago R. Matos Masahiro Hirakawa Masahiro Hirakawa Ana C. Alho Ana C. Alho Ana C. Alho Lars Neleman Luis Graca Jerome Ritz Jerome Ritz Maturation and Phenotypic Heterogeneity of Human CD4+ Regulatory T Cells From Birth to Adulthood and After Allogeneic Stem Cell Transplantation Frontiers in Immunology Treg - regulatory T cell immunology T cell heterogeneity diversity GvHD |
| title | 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_short | 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 |
| topic | Treg - regulatory T cell immunology T cell heterogeneity diversity GvHD |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2020.570550/full |
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