title: Chemotactic migration of T cells towards dendritic cells promotes the detection of rare antigens.
abstract: In many immunological processes chemoattraction is thought to play a role in guiding cells to their sites of action. However, based on in vivo two-photon microscopy experiments in the absence of cognate antigen, T cell migration in lymph nodes (LNs) has been roughly described as a random walk. Although it has been shown that dendritic cells (DCs) carrying cognate antigen in some circumstances attract T cells chemotactically, it is currently still unclear whether chemoattraction of T cells towards DCs helps or hampers scanning. Chemoattraction towards DCs could on the one hand help T cells to rapidly find DCs. On the other hand, it could be deleterious if DCs become shielded by a multitude of attracted yet non-specific T cells. Results from a recent simulation study suggested that the deleterious effect dominates. We re-addressed the question whether T cell chemoattraction towards DCs is expected to promote or hamper the detection of rare antigens using the Cellular Potts Model, a formalism that allows for dynamic, flexible cellular shapes and cell migration. Our simulations show that chemoattraction of T cells enhances the DC scanning efficiency, leading to an increased probability that rare antigen-specific T cells find DCs carrying cognate antigen. Desensitization of T cells after contact with a DC further improves the scanning efficiency, yielding an almost threefold enhancement compared to random migration. Moreover, the chemotaxis-driven migration still roughly appears as a random walk, hence fine-tuned analysis of cell tracks will be required to detect chemotaxis within microscopy data.
authors.affiliation: Theoretical Biology, Utrecht University, Utrecht, The Netherlands.
authors.forename: Renske M A
authors.initials: RM
authors.lastname: Vroomans
authors.forename: Athanasius F M
authors.initials: AF
authors.lastname: Marée
authors.forename: Rob J
authors.initials: RJ
authors.lastname: de Boer
authors.forename: Joost B
authors.initials: JB
authors.lastname: Beltman
mesh_terms: D000941:Antigens / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology*; D002633:Chemotaxis / Q000276:immunology*; D003198:Computer Simulation; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D018448:Models, Immunological; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000941:Antigens; D016207:Cytokines