AUTHOR=Tasnim Humayra , Fricke G. Matthew , Byrum Janie R. , Sotiris Justyna O. , Cannon Judy L. , Moses Melanie E. 

TITLE=Quantitative Measurement of Naïve T Cell Association With Dendritic Cells, FRCs, and Blood Vessels in Lymph Nodes

JOURNAL=Frontiers in Immunology

VOLUME=Volume 9 - 2018

YEAR=2018

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2018.01571

DOI=10.3389/fimmu.2018.01571

ISSN=1664-3224

ABSTRACT=T cells play a vital role in eliminating pathogenic infections. To activate, na¨ıve T cells search
5 lymph nodes (LNs) for dendritic cells (DCs). Positioning and movement of T cells in LNs is
6 influenced by chemokines including CCL21 as well as multiple cell types and structures in the
7 LNs. Some previous studies have suggested that T cell positioning facilitates DC colocalization
8 leading to T:DC interaction. Despite the influence chemical signals, cells, and structures can have
9 on na¨ıve T cell positioning, relatively few studies have used quantitative measures to directly
10 compare T cell interactions with key cell types. Here we use Pearson correlation and normalized
11 mutual information (NMI) to quantify the extent to which na¨ıve T cells spatially associate with DCs,
12 fibroblastic reticular cells (FRCs), and blood vessels in LNs. We measure spatial associations in
13 physiologically relevant regions. We find that T cells are more spatially associated with FRCs
14 than with their ultimate targets, DCs. We also investigated the role of a key motility chemokine
15 receptor, CCR7, on T cell colocalization with DCs. Surprisingly, we find that CCR7 deficiency
16 does not decrease na¨ıve T cells association with DCs, in fact, CCR7-deficient T cells show slightly
17 higher DC association compared with wild type T cells. By revealing these associations, we gain
18 insights into factors that drive T cell localization, potentially affecting the timing of productive T:DC
19 interactions and T cell activation.