Naturally arising memory-phenotype CD4 + T lymphocytes contain an undifferentiated population that can generate T H 1, T H 17, and T reg cells.

Autor: Kawajiri A; Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.; Department of Hematology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan., Li J; Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan., Koinuma K; Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan., Yang Z; Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan., Yoon HJ; Department of Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea., Yi J; Department of Internal Medicine, Division of Rheumatology, Washington University School of Medicine, St. Louis, MO, USA.; Department of Biological Science, Ajou University, Suwon, Republic of Korea., Nagashima H; Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan., Ishii M; Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan., Gao F; Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan., Sato K; Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan., Tayama S; Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan., Harigae H; Department of Hematology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan., Iwakura Y; Center for Animal Disease Models, Research Institute for Biomedical Sciences, Tokyo University of Science, Noda, Chiba, Japan., Ishii N; Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan., Sher A; Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Ishigaki K; Laboratory for Human Immunogenetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan., Zhu J; Molecular and Cellular Immunoregulation Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Kim KS; Department of Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea., Kawabe T; Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.; Molecular and Cellular Immunoregulation Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Jazyk: angličtina
Zdroj: Science advances [Sci Adv] 2024 Dec 06; Vol. 10 (49), pp. eadq6618. Date of Electronic Publication: 2024 Dec 04.
DOI: 10.1126/sciadv.adq6618
Abstrakt: Memory-phenotype (MP) CD4 + T lymphocytes develop from naïve cells via self-recognition at homeostasis. While previous studies defined MP cells as a heterogeneous population that comprises T helper 1 (T H 1)/17-like subsets, functional significance of the T-bet - Rorγt - subpopulation remains unknown. Here we show that MP lymphocytes as a whole population can differentiate into T H 1/17/regulatory T (T reg ) cells to mediate mild and persistent inflammation in lymphopenic environments, whereas naïve cells exhibit strong, T H 1-dominated responses. Moreover, we demonstrate that MP lymphocytes comprise not only T H 1/17-differentiated subsets but a polyclonal, transcriptomically immature "undifferentiated" subpopulation at homeostasis. Furthermore, our data argue that while the T-bet + Rorγt - MP subset is terminally T H 1-differentiated, its undifferentiated counterpart retains the capacity to rapidly proliferate to differentiate into T H 1/17/T reg cells, with the latter response tonically constrained by preexisting T reg cells. Together, our results identify undifferentiated MP CD4 + T lymphocytes as a unique precursor that has a diverse differentiation potential to generate T H 1/17/T reg cells to contribute to pathogenesis of inflammation.
Databáze: MEDLINE
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