Regulation of integrin function by T cell activation - Points of convergence and divergence

Lymphocyte adhesiveness is dynamically regulated in response to conditions in the extracellular environment. One mechanism of regulation of integrin a dhesion receptors involves a rapid, but transient, increase in integrin fun ction upon T lymphocyte activation. These integrin activating signals can b e initiated either via ligation of Ig superfamily members that are coupled to tyrosine kinase cascades, such as the CD3/T cell receptor, CD2, and CD28 , or by G protein-coupled receptors for chemokines. Analysis of integrin ac tivation induced by CD3/TCR, CD2 and CD28 suggests a critical role for phos phoinositide 3-OH kinase (PI 3-K). This review summarizes recent insights i nto PI3-K-dependent regulation of integrin function in leukocytes, includin g the mechanisms by which these receptors are coupled to PI 3-K, and potent ial downstream effecters of PI 3-K that regulate integrin-mediated adhesion in leukocytes.