Polarization diversity of human CD4+ stem cell memory T cells

Masaru Takeshita; Katsuya Suzuki; Yoshiaki Kassai; Maiko Takiguchi; Yusuke Nakayama; Yuki Otomo; Rimpei Morita; Takahiro Miyazaki; Akihiko Yoshimura; Tsutomu Takeuchi

doi:10.1016/j.clim.2015.04.010

Polarization diversity of human CD4⁺ stem cell memory T cells

Masaru Takeshita, Katsuya Suzuki, Yoshiaki Kassai, Maiko Takiguchi, Yusuke Nakayama, Yuki Otomo, Rimpei Morita, Takahiro Miyazaki, Akihiko Yoshimura, Tsutomu Takeuchi

Research output: Contribution to journal › Article › peer-review

27 Citations (Scopus)

Abstract

T cells are considered to develop through three stages, from naïve T (Tn) into central memory T (Tcm) and finally into effector memory T (Tem). Among the subsets of Tn, stem cell memory T (Tscm) were recently found to be the least developed memory subset. While this subset was revealed to possess self-reproducibility and multipotentiality, little is known about the relationship between development and polarity. We conducted transcriptome analysis of human CD4⁺ T subsets and found that Tscm was a clearly distinct subset, located between Tn and Tcm. Surface antigen analysis and differentiation assay showed that the flexibility of polarity and the cytokine production progressively changed as the differentiation of CD4⁺ T cells advanced. Interestingly, we found that most cells of the CD45RO^-CCR7⁺CCR6⁺ subset, hitherto considered the naïve precursor of Th17, were in fact Tscm. These findings may advance our understanding of the highly heterogeneous human helper T cells.

Original language	English
Pages (from-to)	107-117
Number of pages	11
Journal	Clinical Immunology
Volume	159
Issue number	1
DOIs	https://doi.org/10.1016/j.clim.2015.04.010
Publication status	Published - 2015 Jul 1

Keywords

Helper T cell
Stem cell memory T
Th17 precursor

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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10.1016/j.clim.2015.04.010

Cite this

@article{8c663811fb2f46e6b3b14913ca971f1f,

title = "Polarization diversity of human CD4+ stem cell memory T cells",

abstract = "T cells are considered to develop through three stages, from na{\"i}ve T (Tn) into central memory T (Tcm) and finally into effector memory T (Tem). Among the subsets of Tn, stem cell memory T (Tscm) were recently found to be the least developed memory subset. While this subset was revealed to possess self-reproducibility and multipotentiality, little is known about the relationship between development and polarity. We conducted transcriptome analysis of human CD4+ T subsets and found that Tscm was a clearly distinct subset, located between Tn and Tcm. Surface antigen analysis and differentiation assay showed that the flexibility of polarity and the cytokine production progressively changed as the differentiation of CD4+ T cells advanced. Interestingly, we found that most cells of the CD45RO-CCR7+CCR6+ subset, hitherto considered the na{\"i}ve precursor of Th17, were in fact Tscm. These findings may advance our understanding of the highly heterogeneous human helper T cells.",

keywords = "Helper T cell, Stem cell memory T, Th17 precursor",

author = "Masaru Takeshita and Katsuya Suzuki and Yoshiaki Kassai and Maiko Takiguchi and Yusuke Nakayama and Yuki Otomo and Rimpei Morita and Takahiro Miyazaki and Akihiko Yoshimura and Tsutomu Takeuchi",

note = "Funding Information: Yoshiaki Kassai, Maiko Takiguchi, Yusuke Nakayama, and Takahiro Miyazaki are employed by Takeda Pharmaceutical Company Limited. Tsutomu Takeuchi has received grants from Chugai Pharmaceutical Co. Ltd., Pfizer Japan Inc ., and Takeda Pharmaceutical Co. Ltd . Tsutomu Takeuchi has received income from AbbVie GK., Asahi Kasei Medical K.K., Astellas Pharma Inc., Astra Zeneca K.K., Bristol–Myers K.K., Chugai Pharmaceutical Co. Ltd., Daiichi Sankyo Co. Ltd., Eisai Co. Ltd., Eli Lilly Japan K.K., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Co., Novartis Pharma K.K., Pfizer Japan Inc., and Takeda Pharmaceutical Co. Ltd. Funding Information: This work was partly supported by Takeda Pharmaceutical Company Limited, Kanagawa, Japan (grant number 04-078-0067 ). Publisher Copyright: {\textcopyright} 2015 Elsevier Inc. Copyright: Copyright 2019 Elsevier B.V., All rights reserved.",

year = "2015",

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doi = "10.1016/j.clim.2015.04.010",

language = "English",

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T1 - Polarization diversity of human CD4+ stem cell memory T cells

AU - Takeshita, Masaru

AU - Suzuki, Katsuya

AU - Kassai, Yoshiaki

AU - Takiguchi, Maiko

AU - Nakayama, Yusuke

AU - Otomo, Yuki

AU - Morita, Rimpei

AU - Miyazaki, Takahiro

AU - Yoshimura, Akihiko

AU - Takeuchi, Tsutomu

N1 - Funding Information: Yoshiaki Kassai, Maiko Takiguchi, Yusuke Nakayama, and Takahiro Miyazaki are employed by Takeda Pharmaceutical Company Limited. Tsutomu Takeuchi has received grants from Chugai Pharmaceutical Co. Ltd., Pfizer Japan Inc ., and Takeda Pharmaceutical Co. Ltd . Tsutomu Takeuchi has received income from AbbVie GK., Asahi Kasei Medical K.K., Astellas Pharma Inc., Astra Zeneca K.K., Bristol–Myers K.K., Chugai Pharmaceutical Co. Ltd., Daiichi Sankyo Co. Ltd., Eisai Co. Ltd., Eli Lilly Japan K.K., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Co., Novartis Pharma K.K., Pfizer Japan Inc., and Takeda Pharmaceutical Co. Ltd. Funding Information: This work was partly supported by Takeda Pharmaceutical Company Limited, Kanagawa, Japan (grant number 04-078-0067 ). Publisher Copyright: © 2015 Elsevier Inc. Copyright: Copyright 2019 Elsevier B.V., All rights reserved.

PY - 2015/7/1

Y1 - 2015/7/1

N2 - T cells are considered to develop through three stages, from naïve T (Tn) into central memory T (Tcm) and finally into effector memory T (Tem). Among the subsets of Tn, stem cell memory T (Tscm) were recently found to be the least developed memory subset. While this subset was revealed to possess self-reproducibility and multipotentiality, little is known about the relationship between development and polarity. We conducted transcriptome analysis of human CD4+ T subsets and found that Tscm was a clearly distinct subset, located between Tn and Tcm. Surface antigen analysis and differentiation assay showed that the flexibility of polarity and the cytokine production progressively changed as the differentiation of CD4+ T cells advanced. Interestingly, we found that most cells of the CD45RO-CCR7+CCR6+ subset, hitherto considered the naïve precursor of Th17, were in fact Tscm. These findings may advance our understanding of the highly heterogeneous human helper T cells.

AB - T cells are considered to develop through three stages, from naïve T (Tn) into central memory T (Tcm) and finally into effector memory T (Tem). Among the subsets of Tn, stem cell memory T (Tscm) were recently found to be the least developed memory subset. While this subset was revealed to possess self-reproducibility and multipotentiality, little is known about the relationship between development and polarity. We conducted transcriptome analysis of human CD4+ T subsets and found that Tscm was a clearly distinct subset, located between Tn and Tcm. Surface antigen analysis and differentiation assay showed that the flexibility of polarity and the cytokine production progressively changed as the differentiation of CD4+ T cells advanced. Interestingly, we found that most cells of the CD45RO-CCR7+CCR6+ subset, hitherto considered the naïve precursor of Th17, were in fact Tscm. These findings may advance our understanding of the highly heterogeneous human helper T cells.

KW - Helper T cell

KW - Stem cell memory T

KW - Th17 precursor

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