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| Content Provider | frontiers |
|---|---|
| Author | Azarov, Ivan Peskov, Kirill Helmlinger, Gabriel Kosinsky, Yuri |
| Abstract | The adaptive immune response is initiated in lymph nodes by contact between antigen-bearing dendritic cells (DCs) and antigen-specific T cells. A selected number of naïve T cells that recognize a specific antigen may proliferate into expanded clones, differentiate, and acquire an effector phenotype. Despite growing experimental knowledge, certain mechanistic aspects of T cell behavior in lymph nodes remain poorly understood. Computational modeling approaches may help in addressing such gaps. Here we introduce an agent-based model describing T cell movements and their interactions with DCs, leading to activation and expansion of cognate T cell clones, in a two-dimensional representation of the lymph node paracortex. The primary objective was to test the putative role of T cell chemotaxis towards DCs, and quantitatively assess the impact of chemotaxis with respect to T cell priming efficacy. Firstly, we evaluated whether chemotaxis of naïve T cells towards a nearest DC may accelerate the scanning process, by quantifying, through simulations, the number of unique T cell – DC contact events. We demonstrate that, in the presence of naïve T cell-to-DC chemoattraction, a higher total number of contacts occurs, as compared to a T cell random walk scenario. However, the forming swarm of naïve T cells, as these cells get attracted to the neighborhood of a DC, may then physically restrict access of additional T cells to the DC, leading to an actual decrease in the cumulative number of unique contacts between naïve T cells and DCs. Secondly, we investigated the potential role of chemotaxis in maintaining cognate T cell clone expansion. The time course of cognate T cells number in the system was used as a quantitative characteristic of the expansion. Model-based simulations indicate that inclusion of chemotaxis, which is selective for already activated (but not naïve) antigen-specific T cells, may strongly accelerate the time of immune response occurrence, which subsequently increases the overall amplitude of the T cell clone expansion process. |
| ISSN | 16643224 |
| DOI | 10.3389/fimmu.2019.01289 |
| Volume Number | 10 |
| Journal | Frontiers in Immunology |
| Language | English |
| Publisher Date | 2019-06-11 |
| Access Restriction | Open |
| Subject Keyword | Agent-based modeling (ABM) T cells Lymph Node Dendritic Cells Chemotaxis |
| Content Type | Text |
| Resource Type | Article |
| Subject | Immunology and Allergy Immunology |
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