Myosin-IIA and ICAM-1 Regulate the Interchange between Two Distinct Modes of T Cell Migration

Abstract

How T cells achieve rapid chemotactic motility under certain circumstances and efficient cell surface surveillance in others is not fully understood. We show that T lymphocytes are motile in two distinct modes: a fast “amoeboid-like” mode, which uses sequential discontinuous contacts to the substrate; and a slower mode using a single continuously translating adhesion, similar to mesenchymal motility. Myosin-IIA is necessary for fast amoeboid motility, and our data suggests that this occurs via cyclical rear-mediated compressions that eliminate existing adhesions while licensing subsequent ones at the front of the cell. Regulation of Myosin-IIA function in T cells is thus a key mechanism to regulate surface contact area and crawling velocity within different environments. This can provide T lymphocytes with motile and adhesive properties that are uniquely suited toward alternative requirements for immune surveillance and response.

Signal strength regulates antigen-mediated T-cell deceleration by distinct mechanisms to promote local exploration or arrest

“…By dissecting T-cell migration in vitro on chamber slides coated with different substrates (but in the absence of cognate antigen), Krummel and colleagues have identified distinct crawling modes: amoeboid walking on casein-coated surface and haptokinetic sliding on ICAM-1-coated surface (22). Interestingly, the sliding mode was shown to be associated with increased adhesion.…”

Comparison of Immortalized bEnd5 and Primary Mouse Brain Microvascular Endothelial Cells as in vitro Blood–Brain Barrier Models for the Study of T Cell Extravasation

“…A recent two-photon imaging study visualized the intraluminal crawling of encephalitogenic T cells on meningeal microvessels at a higher velocity of 12.5 mm/min in vivo (Bartholomaus et al, 2009). However, in vitro studies of T cell crawling on immobilized ICAM-1 under static conditions (Jacobelli et al, 2009;Smith et al, 2005) documented highly variable T cell crawling velocities that ranged from 4 to 9 mm/min. In particular, the density of ICAM-1 on the crawling substrate (Smith et al, 2005) or the interplay between T cell adhesion and its actomyosin contractility during crawling (Jacobelli et al, 2009) were definitely shown to influence the speed of movement.…”

“…However, in vitro studies of T cell crawling on immobilized ICAM-1 under static conditions (Jacobelli et al, 2009;Smith et al, 2005) documented highly variable T cell crawling velocities that ranged from 4 to 9 mm/min. In particular, the density of ICAM-1 on the crawling substrate (Smith et al, 2005) or the interplay between T cell adhesion and its actomyosin contractility during crawling (Jacobelli et al, 2009) were definitely shown to influence the speed of movement. Thus, different velocities of T cell crawling on brain endothelial cells could be caused by variations in the spatial organization of endothelial cell adhesion molecules.…”

Real-time analysis of T cell receptors in naive cells in vitro and in vivo reveals flexibility in synapse and signaling dynamics

“…In fact, TCR signaling inactivates the contractile machinery necessary for rapid motility by phosphorylating myosin IIA (Jacobelli et al, 2004). Upon myosin IIA inhibition or depletion, T cells maintain an active lamellipodium and slide along in a slow, actin protrusion-dependent mode of motility (Jacobelli et al, 2009). This mode of slow motility during TCR signaling might serve to ensure that the T cell can detect and integrate as many antigen signals as possible by probing as large of an antigen-presenting surface as possible.…”