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Published on: June 20, 2018
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Induction of CD4 T cell memory by local cellular collectivity
Michal Polonsky1, Jacob Rimer1, Amos Kern-Perets1
1Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
Science (New York, N.Y.)
|June 16, 2018
Summary
Cell differentiation involves cells making collective decisions. Naïve CD4+ T cells differentiate into memory precursors when enough cells interact locally, influenced by IL-2 and IL-6.
Area of Science:
- Immunology
- Cell Biology
- Systems Biology
Background:
- Cell differentiation is a fundamental biological process.
- Cell fate decisions can be influenced by cell-cell interactions.
- Understanding T cell differentiation is crucial for adaptive immunity.
Purpose of the Study:
- To investigate the role of collective cell behavior in T cell differentiation.
- To determine the mechanisms by which cell interactions influence memory precursor formation.
- To model the quantitative relationship between cell density and differentiation rate.
Main Methods:
- Live-cell imaging in microwell arrays to observe cell behavior.
- Quantification of cell-cell interactions and differentiation status.
- Analysis of cytokine involvement (IL-2, IL-6) in the process.
- Mathematical modeling to describe the collective differentiation dynamics.
Main Results:
- T cell differentiation into memory precursors increases sharply above a threshold of local cell interactions.
- Homotypic cell interactions, mediated by IL-2 and IL-6, are critical for this collective differentiation.
- These cytokine effects on differentiation are independent of their roles in proliferation and survival.
- Mathematical models confirm that differentiation rate is modulated by the number of interacting cells.
Conclusions:
- Cellular collectivity plays a significant role in directing T cell differentiation towards memory precursors.
- This mechanism allows for the prioritization of immune memory allocation to robust immune responses.
- Collective decision-making in differentiation represents a novel regulatory mechanism in immunology.
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