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Chemotactic migration of T cells towards dendritic cells promotes the detection of rare antigens
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...Show more 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 antigenspecific
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 chemotaxisdriven
migration still roughly appears as a random walk, hence fine-tuned analysis of cell tracks will be required to detect
chemotaxis within microscopy data.Show less
- All authors
- Vroomans, R.M.; Marée, A.F.; Boer, R.J. de; Beltman, J.B.
- Date
- 2012
- Journal
- PLoS Computational Biology
- Volume
- 8
- Issue
- 11
- Pages
- e1002763