Journal
FRONTIERS IN IMMUNOLOGY
Volume 9, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2018.01571
Keywords
mutual information; T cells; dendritic cells; FRCs; CCR7; lymph nodes
Categories
Funding
- DOD STTR Contract [FA8650-18-C-6898]
- NIH [1R01AI097202]
- Spatiotemporal Modeling Center [P50 GM085273]
- Center for Evolution and Theoretical Immunology [5P20GM103452]
- James S. McDonnell Foundation
- UNM Cancer Center Fluorescence Microscopy Facility [P30-CA118100]
- BRAIN Imaging Center [P30GM103400]
- Ruby Predoctoral Travel Fellowship from the Molecular Genetics and Microbiology Department at UNM HSC
- Center of Biomedical Research Excellence (CoBRE) Autophagy, Inflammation, and Metabolism (AIM) in Disease [P20GM121176]
- LDRD grant from Sandia National Laboratories
- [T32 NIH 5 T32 AI007538-19]
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T cells play a vital role in eliminating pathogenic infections. To activate, naive T cells search lymph nodes (LNs) for dendritic cells (DCs). Positioning and movement of T cells in LNs is influenced by chemokines including CCL21 as well as multiple cell types and structures in the LNs. Previous studies have suggested that T cell positioning facilitates DC colocalization leading to T:DC interaction. Despite the influence chemical signals, cells, and structures can have on naive T cell positioning, relatively few studies have used quantitative measures to directly compare T cell interactions with key cell types. Here, we use Pearson correlation coefficient (PCC) and normalized mutual information (NMI) to quantify the extent to which naive T cells spatially associate with DCs, fibroblastic reticular cells (FRCs), and blood vessels in LNs. We measure spatial associations in physiologically relevant regions. We find that T cells are more spatially associated with FRCs than with their ultimate targets, DCs. We also investigated the role of a key motility chemokine receptor, CCR7, on T cell colocalization with DCs. We find that CCR7 deficiency does not decrease naive T cell association with DCs, in fact, CCR7(-/-) T cells show slightly higher DC association compared with wild type T cells. By revealing these associations, we gain insights into factors that drive T cell localization, potentially affecting the timing of productive T: DC interactions and T cell activation.
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