Induction of CD4 T cell memory by local cellular collectivity

• Published in: Science (American Association for the Advancement of Science) Vol. 360; no. 6394
• Main Authors: Polonsky, Michal, Rimer, Jacob, Kern-Perets, Amos, Zaretsky, Irina, Miller, Stav, Bornstein, Chamutal, David, Eyal, Kopelman, Naama Meira, Stelzer, Gil, Porat, Ziv, Chain, Benjamin, Friedman, Nir
• Format: Journal Article
• Language: English
• Published: United States The American Association for the Advancement of Science 15.06.2018
• Subjects: Animals; Antigen-presenting cells; Antigens; CD4 antigen; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes - cytology; CD4-Positive T-Lymphocytes - immunology; Cell activation; Cell density; Cell differentiation; Cell Differentiation - genetics; Cell Differentiation - immunology; Cell growth; Cell number; Cell proliferation; Clusters; Computer applications; Computer Simulation; Cytokines; Decision making; Differentiation (biology); Effector cells; Feedback (Response); Gene Expression; Gene sequencing; Imaging; Immune response; Immune system; Immunologic Memory; Immunological memory; Individualized Instruction; Interleukin 2; Interleukin 6; Interleukin-2 - genetics; Interleukin-2 - immunology; Interleukin-6 - genetics; Interleukin-6 - immunology; L-Selectin - genetics; L-Selectin - immunology; Learning; Lymphocytes; Lymphocytes T; Mathematical analysis; Mathematical models; Memory; Memory cells; Mice; Mice, Inbred C57BL; Mice, Transgenic; Models, Immunological; Participative Decision Making; Population density; Population studies; Precursors; Priming; Quorum Sensing - immunology; Ribonucleic acid; RNA; Sensitivity; Sequence Analysis, RNA; Signal processing; Signaling Lymphocytic Activation Molecule Family - immunology; Social behavior; T cell receptors; Tracking; Trajectory analysis
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.aaj1853

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 naïve CD4 T cells into memory precursors. We found that differentiation of precursor memory T cells 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.