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

作者：Akihisa Kawajiri, Jing Li, Keita Koinuma, Ziying Yang, Hye Jin Yoon, Jaeu Yi, Hiroyuki Nagashima, Minami Ishii, Feng Gao, Kosuke Sato, Shunichi Tayama, Hideo Harigae, Yoichiro Iwakura, Naoto Ishii, Alan Sher, Kazuyoshi Ishigaki, Jinfang Zhu, Kwang Soon Kim, Takeshi Kawabe · 发表于：Science Advances · 年份：2024 · DOI：10.1126/sciadv.adq6618 · 被引用次数：6 · 研究领域：T-cell and B-cell Immunology、Immune Cell Function and Interaction、IL-33, ST2, and ILC Pathways

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.