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 toward DCs, and quantitatively assess the impact of chemotaxis with respect to T cell priming efficacy. Firstly, we evaluated whether chemotaxis of naïve T cells toward 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.
Highlights
After maturation in the thymus, immunologically-naïve T lymphocytes continuously circulate between the blood and secondary lymphoid organs, including lymphatic nodes (LNs) and the spleen
Our first goal was to explore the impact of chemoattraction upon efficiency in the process of T cell repertoire scanning, as naïve T cells moved toward a dendritic cells (DCs)
The measure of such efficacy was computed as the rate of accumulation of unique T cell— DC contact events
Summary
After maturation in the thymus, immunologically-naïve T lymphocytes (or T cells) continuously circulate between the blood and secondary lymphoid organs, including lymphatic nodes (LNs) and the spleen. In LNs, naïve T cells may encounter dendritic cells (DCs) presenting cognate antigens as MHC-bound peptides (pMHC) on their surface. As a result of such a specific and durable contact T cell-to-DC contact, a naïve T cell may become activated and subsequently proliferate and differentiate into effector forms. This constitutes, in most simplified terms, the essence of the immune response. Since most naïve T cells feature irrelevant specificities, the probability of an immediate contact between a DC bearing a particular antigen and a cognate T cell appears to be very low. For efficient antigen recognition, each DC should be in a position to scan a large number of T cells with differing specificities
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
