First Author | Nish SA | Year | 2017 |
Journal | J Exp Med | Volume | 214 |
Issue | 1 | Pages | 39-47 |
PubMed ID | 27923906 | Mgi Jnum | J:238782 |
Mgi Id | MGI:5824156 | Doi | 10.1084/jem.20161046 |
Citation | Nish SA, et al. (2017) CD4+ T cell effector commitment coupled to self-renewal by asymmetric cell divisions. J Exp Med 214(1):39-47 |
abstractText | 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. |