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Chemotactic Migration of T Cells towards Dendritic Cells Promotes the Detection of Rare Antigens

Vroomans, R.M.A., Maree, A.F.M., de Boer, R.J. and Beltman, J.B. 2012. Chemotactic Migration of T Cells towards Dendritic Cells Promotes the Detection of Rare Antigens. PLoS Computational Biology 8 (11) , -. 10.1371/journal.pcbi.1002763

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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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Publisher: Public Library of Science
ISSN: 1553-734X
Date of Acceptance: 14 September 2012
Last Modified: 18 Feb 2019 08:31
URI: https://orca.cardiff.ac.uk/id/eprint/119520

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