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


FULLTEXT
Published:
01.29.2019
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Last Revised:
03.05.2019
PMID:
30093900
Frontiers in immunology
Journal Article,Research Support, N.I.H., Extramural,Research Support, Non-U.S. Gov't,Research Support, U.S. Gov't, Non-P.H.S.

Moses Biological Computation Laboratory, Department of Computer Science, The University of New Mexico, Albuquerque, NM, United States.
Moses Biological Computation Laboratory, Department of Computer Science, The University of New Mexico, Albuquerque, NM, United States.,UNM Center for Advanced Research Computing (CARC), The University of New Mexico, Albuquerque, NM, United States.
The Cannon Laboratory, Molecular Genetics & Microbiology, The University of New Mexico, Albuquerque, NM, United States.
Moses Biological Computation Laboratory, Department of Computer Science, The University of New Mexico, Albuquerque, NM, United States.
The Cannon Laboratory, Molecular Genetics & Microbiology, The University of New Mexico, Albuquerque, NM, United States.,Department of Pathology, The University of New Mexico, Albuquerque, NM, United States.,Autophagy, Inflammation, and Metabolism Center of Biomedical Research Excellence, The University of New Mexico, Albuquerque, NM, United States.
Moses Biological Computation Laboratory, Department of Computer Science, The University of New Mexico, Albuquerque, NM, United States.,Biology Department, The University of New Mexico, Albuquerque, NM, United States.,Santa Fe Institute, Santa Fe, NM, United States.

Abstract

T cells play a vital role in eliminating pathogenic infections. To activate, naïve 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 naïve 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 naïve 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 naïve 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.

GrantID: P30 CA118100, Acronym: CA, Agency: NCI NIH HHS, Country: United States | GrantID: R01 AI097202, Acronym: AI, Agency: NIAID NIH HHS, Country: United States | GrantID: P30 GM110907, Acronym: GM, Agency: NIGMS NIH HHS, Country: United States | GrantID: P20 GM103452, Acronym: GM, Agency: NIGMS NIH HHS, Country: United States | GrantID: R25 GM060201, Acronym: GM, Agency: NIGMS NIH HHS, Country: United States | GrantID: P20 GM121176, Acronym: GM, Agency: NIGMS NIH HHS, Country: United States | GrantID: T32 AI007538, Acronym: AI, Agency: NIAID NIH HHS, Country: United States | GrantID: P50 GM085273, Acronym: GM, Agency: NIGMS NIH HHS, Country: United States | GrantID: P30 GM103400, Acronym: GM, Agency: NIGMS NIH HHS, Country: United States