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4
1- and 51-mediated Function
Leukocyte Adhesion Laboratory, Imperial Cancer Research Fund, Lincoln's Inn Fields, London WC2A 3PX, United Kingdom
A regulated order of adhesion events directs
leukocytes from the vascular compartment into injured
tissues in response to inflammatory stimuli. We show
that on human T cells, the interaction of the 
2 integrin
leucocyte function-associated antigen-1 (LFA-1) with
its ligand intercellular adhesion molecule-1 (ICAM-1)
will decrease adhesion mediated by 
41 and, to a
lesser extent, 51. Similar inhibition is also seen when
T cells are exposed to mAb 24, which stabilizes LFA-1
in an active state after triggering integrin function
through divalent cation Mg2+, PdBu, or T cell receptor/
CD3 complex (TCR/CD3) cross-linking. Such cross
talk decreases 41 integrin-mediated binding of T cells to fibronectin and vascular cell adhesion molecule-1
(VCAM-1). In contrast, ligand occupancy or prolonged
activation of 1 integrin has no effect on LFA-1 adhesion to ICAM-1. We also show that T cell migration
across fibronectin, unlike adhesion, is mediated solely
by 51, and is increased when the 41-mediated
component of fibronectin adhesion is decreased either
by cross talk or the use of 4-blocking mAb. The ability
of mAb 24 Fab
fragments to induce cross talk without
cross-linking LFA-1 suggests signal transduction
through the active integrin. These data provide the first
direct evidence for cross talk between LFA-1 and 1 integrins on T cells. Together, these findings imply that
activation of LFA-1 on the extravasating T cell will decrease the binding to VCAM-1 while enhancing the
subsequent migration on fibronectin. This sequence of
events provides a further level of complexity to the coordination of T cell integrins, whose sequential but overlapping roles are essential for transmigration.
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