Abstract
Secondary lymphoid organs (SLO), such as lymph nodes and the spleen, display a complex micro-architecture. In the T cell zone the micro-architecture is provided by a network of fibroblastic reticular cells (FRC) and their filaments. The FRC network is thought to enhance the interaction between immune cells and their cognate antigen. However, the effect of the FRC network on cell interaction cannot be quantified to date because of limitations in immunological methodology. We use computational models to study the influence of different densities of FRC networks on the probability that two cells meet. We developed a 3D cellular automaton model to simulate cell movements and interactions along the FRC network inside lymphatic tissue. We show that the FRC network density has only a small effect on the probability of a cell to come into contact with a static or motile target. However, damage caused by a disruption of the FRC network is greatest at FRC densities corresponding to densities observed in the spleen of naïve mice. Our analysis suggests that the FRC network as a guiding structure for moving T cells has only a minor effect on the probability to find a corresponding dendritic cell. We propose alternative hypotheses by which the FRC network might influence the functionality of immune responses in a more significant way.
Highlights
Secondary lymphoid organs (SLOs), such as lymph nodes (LN) or the spleen, are anatomical structures important for the establishment and proper functioning of immune responses
The lymphoid chemokines CCL19 and CCL21, which interact with the CCR7 receptor on naıve T cells and activated dendritic cells, and other soluble factors presented by fibroblastic reticular cells (FRC) influence T cell motility in lymph nodes [16,17,18]
The interaction between lymphocytes and antigen presenting cells or infected cells is thought to be enhanced by the complex microarchitecture of secondary lymphoid organs such as the spleen or lymph nodes
Summary
Secondary lymphoid organs (SLOs), such as lymph nodes (LN) or the spleen, are anatomical structures important for the establishment and proper functioning of immune responses. Developed two-photon microscopy methods enable us to observe how the cells move inside of LNs and the spleen ex vivo or in vivo [5,6,7,8,9,10] Using this method, it has been observed that lymphocytes move along the fibroblastic reticular cell (FRC) network – a network formed by FRC and filaments between them [11]. The lymphoid chemokines CCL19 and CCL21, which interact with the CCR7 receptor on naıve T cells and activated dendritic cells, and other soluble factors presented by FRCs influence T cell motility in lymph nodes [16,17,18]. Dendritic cells tend to reside on FRCs [19,20]
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