Year: 2016
Type: article
Abstract: Upon infection, an activated CD4+ T cell produces terminally differentiated effector cells and renews itself for continued defense. In this study, we show that differentiation and self-renewal arise as opposing outcomes of sibling CD4+ T cells. After influenza challenge, antigen-specific cells underwent several divisions in draining lymph nodes (LN; DLNs) while maintaining expression of TCF1. After four or five divisions, some cells silenced, whereas some cells maintained TCF1 expression. TCF1-silenced cells were T helper 1–like effectors and concentrated in the lungs. Cells from earliest divisions were memory-like and concentrated in nondraining LN. TCF1-expressing cells from later divisions in the DLN could self-renew, clonally yielding a TCF1-silenced daughter cell as well as a sibling cell maintaining TCF1 expression. Some TCF1-expressing cells in DLNs acquired an alternative, follicular helper-like fate. Modeled differentiation experiments in vitro suggested that unequal PI3K/mechanistic target of rapamycin signaling drives intraclonal cell fate heterogeneity. Asymmetric division enables self-renewal to be coupled to production of differentiated CD4+ effector T cells during clonal selection.
DOI: 10.1084/jem.20161046
Authors: Simone A. Nish, Kyra D. Zens, Radomir Kratchmarov, Wen-Hsuan W. Lin, William C. Adams, Yen-Hua Chen, Bonnie Yen, Nyanza J. Rothman, Avinash Bhandoola, Hai-Hui Xue, Donna L. Farber, Steven L. Reiner
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: hybrid
Awards: G1543716854, G1833045553, G251338959, G3241252221, Molecular mechanisms controlling differentiation of memory CD8 T cells, G5825260925, G635834282, G6808003070, G7188297838, Self-renewing Lymphocyte Division in The Immune Response, G8515830085, G892472763, G89973260, G9000003511, G9000052810, G9000071715, G9000118321, G9000155343, G9000200958, G9000300037, Cancer Center Support Grant
OpenAlex ID: W2560111197