A role for LFA-1 in delaying T-lymphocyte egress from lymph nodes

Abstract

Lymphocytes use the integrin leukocyte functionassociated antigen-1 (LFA-1) to cross the vasculature into lymph nodes (LNs), but it has been uncertain whether their migration within LN is also LFA-1 dependent. We show that LFA-1 mediates prolonged LN residence ashosts lacking the major LFA-1 ligand ICAM-1. Intra-vital two-photon microscopy revealed that LFA-1 þ / þ and LFA-1 À / À T cells reacted differently when probing the ICAM-1-expressing lymphatic network. While LFA-1T cells returned to the LN parenchyma with greater frequency, LFA-1 À / À T cells egressed promptly. This difference in exit behaviour was a feature of egress through all assessed lymphatic exit sites. We show that use of LFA-1 as an adhesion receptor amplifies the number of T cells returning to the LN parenchyma that can lead to increased effectiveness of T-cell response to antigen. Thus, we identify a novel function for LFA-1 in guiding T cells at the critical point of LN egress when they either exit or return into the LN for further interactions.

T Cell–Independent Modulation of Experimental Autoimmune Encephalomyelitis in ADAP-Deficient Mice

“…This might induce a stronger adhesion of the T cells to the lymphatic endothelial cells, thereby preventing their egress from the lymph node. Indeed, we recently observed that the interaction between LFA-1 expressed by lymph node T cells and ICAM-1 expressed by lymphatic vessels determines the egress rate of T cells from the lymph nodes (50). We are currently setting up the experimental systems to evaluate this possibility.…”

The multiple faces of leukocyte interstitial migration

“…Since naïve T cells express the integrins LFA-1 and α4β1, CCL21-binding FRCs might serve as excellent adhesive substrate. It was therefore surprising when several groups observed prominent T cell motility with only minimal changes in speed (10–30 % reduction) when integrin function was perturbed by gene deletions or functional antibody blockade [37, 169–171]. Based on these experiments, it was concluded that LFA-1 is only minimally engaged during T cell migration in lymph nodes, probably because of missing shear flow that could activate integrins.…”

“…In conclusion, basal T cell motility in lymph nodes does not require integrin-mediated forces, but LFA-1 engagement promotes a 10–40 % faster motility mode along two superposed ICAM-1- and CCL21-decorated cellular networks (DCs and FRCs). This might allow T cells to increase their scanning area and efficiency, but also to mediate prolonged residency in the lymph node paracortex, where LFA-1/ICAM-1 interactions have been shown to counteract early lymph node egress into medullary sinuses [171]. …”

T cell-intrinsic S1PR1 regulates endogenous effector T-cell egress dynamics from lymph nodes during infection

“…T-cell entry into the LN is controlled by G protein-coupled receptors (GPCRs) (3) such as CC chemokine receptor 7 (CCR7), which is also critical for the localization and retention of T cells within the LN paracortex (5,6). Egress of naive T cells from the LN via the lymphatic vessels is regulated by the GPCR sphingosine-1-phosphate receptor-1 (S1PR1) (3) and adhesion molecules (4). S1PR1 is among four other GPCRs that bind to sphingosine-1-phosphate (S1P) with high affinity.…”