Polarization diversity of human CD4+ stem cell memory T cells.
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.
Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. Electronic address: takeshita@a5.keio.jp.
Masaru
M
Takeshita
Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. Electronic address: katsuyas@z5.keio.jp.
Katsuya
K
Suzuki
Inflammation Drug Discovery Unit, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 26-1, Muraoka-Higashi 2-Chome, Fujisawa-Shi, Kanagawa 251-8555, Japan. Electronic address: yoshiaki.kassai@takeda.com.
Yoshiaki
Y
Kassai
Inflammation Drug Discovery Unit, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 26-1, Muraoka-Higashi 2-Chome, Fujisawa-Shi, Kanagawa 251-8555, Japan. Electronic address: maiko.takiguchi@takeda.com.
Maiko
M
Takiguchi
Integrated Technology Research Laboratories, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 26-1, Muraoka-Higashi 2-Chome, Fujisawa-shi, Kanagawa 251-8555, Japan. Electronic address: yuusuke.nakayama@takeda.com.
Yusuke
Y
Nakayama
Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. Electronic address: yukiootomo@a7.keio.jp.
Yuki
Y
Otomo
Department of Microbiology and Immunology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. Electronic address: rimpeim@a7.keio.jp.
Rimpei
R
Morita
Inflammation Drug Discovery Unit, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 26-1, Muraoka-Higashi 2-Chome, Fujisawa-Shi, Kanagawa 251-8555, Japan. Electronic address: takahiro.miyazaki@takeda.com.
Takahiro
T
Miyazaki
Department of Microbiology and Immunology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. Electronic address: yoshimura@a6.keio.jp.
Akihiko
A
Yoshimura
Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. Electronic address: tsutake@z5.keio.jp.
Tsutomu
T
Takeuchi
D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D002454:Cell Differentiation; D016764:Cell Polarity; D006801:Humans; D007156:Immunologic Memory; D017493:Leukocyte Common Antigens / Q000378:metabolism; D054399:Receptors, CCR6 / Q000378:metabolism; D054400:Receptors, CCR7 / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000378:metabolism; D058504:Th17 Cells / Q000166:cytology / Q000378:metabolism
C106311:CCR6 protein, human; C515370:CCR7 protein, human; D054399:Receptors, CCR6; D054400:Receptors, CCR7; D017493:Leukocyte Common Antigens
Helper T cell; Stem cell memory T; Th17 precursor