How T cells avoid traffic jams

JEREMY POSTAT; INGE WORTEL; PARISI, DANIEL R.; JOHANNES TEXTOR; JUDITH MANDL

Encuentro VIRTUAL por pandemia

Conferencia; 20th HFSP Awardees Meeting; 2021

HFSP

T cells are continually in motion. Both at homeostasis and during infection, crowds of T cells move through tissues to survey for antigen or to contribute to an immune response. From other systems - such as pedestrian traffic, grain silos, and cellular monolayers - we know that crowding can hinder motion by causing jams. Yet T cells defy this general principle and can move fluidly even in extremely dense environments such as lymphatic tissue and the epidermis, where there is no apparent room to maneuver. How they achieve this is unclear: although novel microscopy modalities can visualize migrating T cells in living tissue, studies of T cell movement have primarily focused on individual or few cells and have not addressed potential crowding effects.Here we borrow concepts and approaches from the crowd dynamics field to uncover basic properties of T cell crowd dynamics, combining in silico modeling and in vitro experiments in microfabricated devices. In single-lane traffic, a cornerstone scenario of crowd dynamics research, our simulations using a Cellular Potts Model predicted that T cell motion is barely hampered by high densities, a finding confirmed by our experimental results. This remarkable resilience to jamming sets T cell crowds apart from cellular monolayers or pedestrians, and resembles the behavior of social collectives such as ant colonies.By investigating T cells as a crowding system, our work establishes a link between the fields of T cell immunology and traffic theory. Our simulations will now allow us to probe for known crowding phenomena that cannot be experimentally measured. Understanding how and under which conditions T cells can avoid crowding issues will be crucial to uncover how malignancies and infectious diseases impact T cell migration.