Persistence and Adaptation in Immunity: T Cells Balance the Extent and Thoroughness of Search

Abstract

Effective search strategies have evolved in many biological systems, including the immune system. T cells are key effectors of the immune response, required for clearance of pathogenic infection. T cell activation requires that T cells encounter antigen-bearing dendritic cells within lymph nodes, thus, T cell search patterns within lymph nodes may be a crucial determinant of how quickly a T cell immune response can be initiated. Previous work suggests that T cell motion in the lymph node is similar to a Brownian random walk, however, no detailed analysis has definitively shown whether T cell movement is consistent with Brownian motion. Here, we provide a precise description of T cell motility in lymph nodes and a computational model that demonstrates how motility impacts T cell search efficiency. We find that both Brownian and Lévy walks fail to capture the complexity of T cell motion. Instead, T cell movement is better described as a correlated random walk with a heavy-tailed distribution of step lengths. Using computer simulations, we identify three distinct factors that contribute to increasing T cell search efficiency: 1) a lognormal distribution of step lengths, 2) motion that is directionally persistent over short time scales, and 3) heterogeneity in movement patterns. Furthermore, we show that T cells move differently in specific frequently visited locations that we call “hotspots” within lymph nodes, suggesting that T cells change their movement in response to the lymph node environment. Our results show that like foraging animals, T cells adapt to environmental cues, suggesting that adaption is a fundamental feature of biological search.

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“…In addition, agent-based simulations depicted that the lognormal modulated PRW has the maximum compliance with the observed efficiency of migrating T cells, following dendritic cells. This migration behavior presents a balance between the accuracy and amount of distance traveled by the cells [72]. Moreover, the findings confirm the hypothesis of migration heterogeneity among the T-lymphocyte population [64].…”

Tissue-resident T cell–derived cytokines eliminate herpes simplex virus-2–infected cells

“…When cognate antigen is not present, Trm cells patrol the cellular grid ( Figure 5A and ref. 44). Recent evidence provides rates for Trm cell movement and suggests that trafficking follows a random walk over time scales of hours (1,22).…”

Hybrid approach to model the spatial regulation of T cell responses

“…The motility of T cells in the lymph node is determined by their random motion and mechanical cell-cell interactions [40]. The spatial distribution of cytokines considered in the model (IL-2 and type I IFN), though it requires more detailed investigation, corresponds to the actual understanding of the role of these cytokines.…”