Quantitative analyses of T cell motion in tissue reveals factors driving T cell search in tissues
Abstract
T cells are required to clear infection, moving first in lymph nodes to interact with antigen bearing dendritic cells leading to activation. T cells then move to sites of infection to find and clear infection. T cell motion plays a role in how quickly a T cell finds its target, from initial natiıve T cell activation by a dendritic cell to interaction with target cells in infected tissue. To better understand how different tissue environments might affect T cell motility, we compared multiple features of T cell motion including speed, persistence, turning angle, directionality, and confinement of motion from T cells moving in multiple tissues using tracks collected with microscopy from murine tissues. We quantitatively analyzed natiıve T cell motility within the lymph node and compared motility parameters with activated CD8 T cells moving within the villi of small intestine and lung under different activation conditions. Our motility analysis found that while the speeds and the overall displacement of T cells vary within all tissues analyzed, T cells in all tissues tended to persist at the same speed, particularly if the previous speed is very slow (less than 2 μm/min) or very fast (greater than 8 μm/min) with the exception of T cells in the villi for speeds greater than 10 μm/min. Interestingly, we found that turning angles of T cells in the lung show a marked population of T cells turning at close to 180o, while T cells in lymph nodes and villi do not exhibit this 'reversing' movement. Additionally, T cells in the lung showed significantly decreased meandering ratios and increased confinement compared to T cells in lymph nodes and villi. The combination of these differences in motility patterns led to a decrease in the total volume scanned by T cells in lung compared to T cells in lymph node and villi. These results suggest that the tissue environment in which T cells move can impact the type of motility and ultimately, the efficiency of T cell search for target cells within specialized tissues such as the lung.
Data availability
Datasets are available as Supplementary Materials under the Biorxiv preprint BIORXIV/2022/516891 https://www.biorxiv.org/content/10.1101/2022.11.17.516891v2.supplementary-material. The code used for analysis can be downloaded at: https://github.com/davytorres/T-cell-analysis-tool .
Article and author information
Author details
Funding
National Institutes of Health (P20GM103451)
- David J Torres
University of New Mexico (NCI P30CA118100)
- Paulus Mrass
National Institutes of Health (P20GM121176)
- Paulus Mrass
University of New Mexico (School of Medicine)
- Paulus Mrass
National Institutes of Health (1R01AI097202)
- Judy L Cannon
National Institutes of Health (P50 GM085273)
- Judy L Cannon
National Institutes of Health (5P20GM103452)
- Judy L Cannon
National Institutes of Health (P20GM121176)
- Judy L Cannon
National Institutes of Health (5 T32 AI007538-19)
- Janie Byrum
University of New Mexico (School of Medicine)
- Judy L Cannon
University of New Mexico (DARPA/AFRL FA8650-18-C-6898)
- Judy L Cannon
University of New Mexico (NCI P30CA118100)
- Judy L Cannon
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All work was done in accordance with approved protocols per IACUC institutional approvals, IACUC Animal approval #: 21-201165-HS
Copyright
© 2023, Torres et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 1,139
- views
-
- 158
- downloads
-
- 3
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Further reading
-
- Biochemistry and Chemical Biology
- Computational and Systems Biology
Protein–protein interactions are fundamental to understanding the molecular functions and regulation of proteins. Despite the availability of extensive databases, many interactions remain uncharacterized due to the labor-intensive nature of experimental validation. In this study, we utilized the AlphaFold2 program to predict interactions among proteins localized in the nuage, a germline-specific non-membrane organelle essential for piRNA biogenesis in Drosophila. We screened 20 nuage proteins for 1:1 interactions and predicted dimer structures. Among these, five represented novel interaction candidates. Three pairs, including Spn-E_Squ, were verified by co-immunoprecipitation. Disruption of the salt bridges at the Spn-E_Squ interface confirmed their functional importance, underscoring the predictive model’s accuracy. We extended our analysis to include interactions between three representative nuage components—Vas, Squ, and Tej—and approximately 430 oogenesis-related proteins. Co-immunoprecipitation verified interactions for three pairs: Mei-W68_Squ, CSN3_Squ, and Pka-C1_Tej. Furthermore, we screened the majority of Drosophila proteins (~12,000) for potential interaction with the Piwi protein, a central player in the piRNA pathway, identifying 164 pairs as potential binding partners. This in silico approach not only efficiently identifies potential interaction partners but also significantly bridges the gap by facilitating the integration of bioinformatics and experimental biology.
-
- Computational and Systems Biology
- Neuroscience
Accumulating evidence to make decisions is a core cognitive function. Previous studies have tended to estimate accumulation using either neural or behavioral data alone. Here, we develop a unified framework for modeling stimulus-driven behavior and multi-neuron activity simultaneously. We applied our method to choices and neural recordings from three rat brain regions—the posterior parietal cortex (PPC), the frontal orienting fields (FOF), and the anterior-dorsal striatum (ADS)—while subjects performed a pulse-based accumulation task. Each region was best described by a distinct accumulation model, which all differed from the model that best described the animal’s choices. FOF activity was consistent with an accumulator where early evidence was favored while the ADS reflected near perfect accumulation. Neural responses within an accumulation framework unveiled a distinct association between each brain region and choice. Choices were better predicted from all regions using a comprehensive, accumulation-based framework and different brain regions were found to differentially reflect choice-related accumulation signals: FOF and ADS both reflected choice but ADS showed more instances of decision vacillation. Previous studies relating neural data to behaviorally inferred accumulation dynamics have implicitly assumed that individual brain regions reflect the whole-animal level accumulator. Our results suggest that different brain regions represent accumulated evidence in dramatically different ways and that accumulation at the whole-animal level may be constructed from a variety of neural-level accumulators.