Journal
SCIENCE
Volume 360, Issue 6394, Pages 1201-+Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aaj1853
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Funding
- Israel Science Foundation [1184/15]
- Israel Ministry of Science, Technology and Space
- German Cancer Research Center (DKFZ)
- Weizmann UK foundation
- Weston Visiting Professorship from the Weizmann Institute of Science
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Cell differentiation is directed by signals driving progenitors into specialized cell types. This process can involve collective decision-making, when differentiating cells determine their lineage choice by interacting with each other. We used live-cell imaging in microwell arrays to study collective processes affecting differentiation of naive CD4+ Tcells into memory precursors. We found that differentiation of precursor memory Tcells sharply increases above a threshold number of locally interacting cells. These homotypic interactions involve the cytokines interleukin-2 (IL-2) and IL-6, which affect memory differentiation orthogonal to their effect on proliferation and survival. Mathematical modeling suggests that the differentiation rate is continuously modulated by the instantaneous number of locally interacting cells. This cellular collectivity can prioritize allocation of immune memory to stronger responses.
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