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

Front Immunol. 2018 Jul 26:9:1571. doi: 10.3389/fimmu.2018.01571. eCollection 2018.

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.

Keywords: CCR7; FRCs; T cells; dendritic cells; lymph nodes; mutual information.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cell Communication / immunology
  • Chemokine CCL21 / immunology
  • Cytokines / immunology
  • Data Interpretation, Statistical
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology*
  • Fibroblasts / cytology
  • Fibroblasts / immunology*
  • Humans
  • Lymph Nodes / cytology
  • Lymph Nodes / immunology*
  • Lymphocyte Activation
  • Mice
  • Models, Animal
  • Receptors, CCR7 / immunology
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*

Substances

  • CCL21 protein, human
  • Chemokine CCL21
  • Cytokines
  • Receptors, CCR7