Maturation and Phenotypic Heterogeneity of Human CD4+ Regulatory T Cells From Birth to Adulthood and After Allogeneic Stem Cell Transplantation.
Maturation and Phenotypic Heterogeneity of Human CD4+ Regulatory T Cells From Birth to Adulthood and After Allogeneic Stem Cell Transplantation.
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DOI：
10.3389/fimmu.2020.570550
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发表时间：
2020
影响因子：
7.3
通讯作者：
Ritz J
中科院分区：
文献类型：
--
作者：
Matos TR;Hirakawa M;Alho AC;Neleman L;Graca L;Ritz J
CD4+调节性T细胞（Treg）在维持免疫稳态中起关键作用。已经鉴定了各种Treg亚群，然而发育期间Treg亚群的异质性仍然没有表征。使用质谱细胞术，我们获得了35个功能标志物表达的单细胞数据，以检查出生时和成人Treg细胞的异质性。使用无监督聚类算法FlowSOM和ACCENSE来量化Treg异质性。正如预期的那样，脐带血中的Treg主要是幼稚的，而成人血液中的Treg主要是中枢记忆和效应记忆细胞。虽然脐带血Treg大多是幼稚细胞，但我们在脐带血中观察到多种表型Treg亚群。然而，成人外周血中含有较高百分比的Treg，并且Treg的异质性在成人中显著增加。我们还研究了异基因造血干细胞移植（alloHSCT）后2年期间和慢性移植物抗宿主病（cGVHD）患者的Treg异质性。Treg异质性在alloHSCT后迅速恢复，并在移植后的前两年逐渐增加。然而，患有cGVHD的患者具有显著更少的不同Treg亚群，这表明Treg异质性被破坏与cGVHD之间存在相关性。我们的研究是第一个比较人类Treg异质性在出生时，在健康成人和alloHSCT后的患者与不cGVHD。这种基于一大组功能标记物的表达来表征Treg异质性的方法可能使未来的研究能够鉴定导致免疫功能障碍的特定Treg缺陷。
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.
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DOI：
10.1073/pnas.1321405111
发表时间：
2014-01-07
影响因子：
11.1
作者：
Shekhar, Karthik;Brodin, Petter;Chakraborty, Arup K.
通讯作者：
Chakraborty, Arup K.
DOI：
10.1126/science.1198704
发表时间：
2011-05-06
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Bendall SC;Simonds EF;Qiu P;Amir el-AD;Krutzik PO;Finck R;Bruggner RV;Melamed R;Trejo A;Ornatsky OI;Balderas RS;Plevritis SK;Sachs K;Pe'er D;Tanner SD;Nolan GP
通讯作者：
Nolan GP
供体型CD4（+）CD25（+）调节性T细胞在同种异体骨髓移植后抑制致命的急性移植物抗宿主疾病。
影响因子：
15.3
作者：
Hoffmann, Petra;Ermann, Joerg;Edinger, Matthias;Fathman, C Garrison;Strober, Samuel
通讯作者：
Strober, Samuel
影响因子：
64.8
作者：
Sallusto, F;Lenig, D;Lanzavecchia, A
通讯作者：
Lanzavecchia, A
DOI：
10.1056/nejmoa1108188
发表时间：
2011-12-01
期刊：
The New England journal of medicine
影响因子：
--
作者：
Koreth J;Matsuoka K;Kim HT;McDonough SM;Bindra B;Alyea EP 3rd;Armand P;Cutler C;Ho VT;Treister NS;Bienfang DC;Prasad S;Tzachanis D;Joyce RM;Avigan DE;Antin JH;Ritz J;Soiffer RJ
通讯作者：
Soiffer RJ