 Chemotactic Migration of T Cells towards Dendritic Cells Promotes the Detection of Rare AntigensRenske M A Vroomans, Athanasius F M Marée, Rob J de Boer and Joost B Beltman PLOS Computational Biology, 2012, vol. 8, issue 11, 1-13 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. Author Summary: T lymphocytes are important actors of the immune system that find and kill infected cells. Before a T cell can mount such an immune response, it has to be activated through contact with a dendritic cell (DC) carrying antigen relevant to the specificity of the T cell receptor. This process typically takes place in secondary lymphoid organs such as lymph nodes and spleen, where DCs scan many T cells at a time. However, the fraction of T cells specific for any antigen is about –, and therefore establishing a contact between a DC carrying cognate antigen and the correct T cells seems quite a challenge. Here, we show with a computational model that despite the presence of millions of competing non-specific T cells, the probability of such a cognate interaction greatly increases when DCs produce a chemokine ligand to attract T cells. The scanning process becomes even more efficient when T cells become insensitive to the chemokine after contacting the DC. These findings oppose the earlier notion that chemoattraction is counterproductive due to blocking of DCs by T cells of irrelevant specificities. Date: 2012 Downloads: (external link) Related works: Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text Persistent link: https://EconPapers.repec.org/RePEc:plo:pcbi00:1002763 DOI: 10.1371/journal.pcbi.1002763 Access Statistics for this article More articles in PLOS Computational Biology from Public Library of Science |
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