No abstract

Lymphocyte adhesiveness is dynamically regulated in response to conditions in the extracellular environment. One mechanism of regulation of integrin adhesion receptors involves a rapid, but transient, increase in integrin function upon T lymphocyte activation. These integrin activating signals can be 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 activation induced by CD3/TCR, CD2 and CD28 suggests a critical role for phosphoinositide 3-OH kinase (PI 3-K). This review summarizes recent insights into PI 3-K-dependent regulation of integrin function in leukocytes, including the mechanisms by which these receptors are coupled to PI 3-K, and potential downstream effectors of PI 3-K that regulate integrin-mediated adhesion in leukocytes.

T-lymphocyte movement out of the bloodstream and into tissue is critical to the success of these cells in their role in immunosurveillance. This process involves interactions of the T-cell with endothelium as well as with extracellular matrix. Central to these interactions are a number of T-cell adhesion molecules and their endothelial and extracellular matrix ligands. The identification and functional characterization of adhesion molecules have been the subject of intensive research in recent years. We highlight here the latest developments in this rapidly expanding field as they pertain to T-cell interactions with endothelial cells and extracellular matrix components, including: (1) identification of adhesion molecule families, including the selectins, mucins, integrins, immunoglobulin superfamily members, and cadherins; (2) elucidation of the multi-step adhesion cascade that mediates the rolling, arrest, and eventual diapedesis of T-cells through the vascular endothelium into the surrounding tissue; (3) the changes in adhesion molecule expression that accompany T-cell maturation and activation, and the impact of those changes on T-cell migration; (4) the functional relevance of the extracellular matrix for T-cell function; and (5) the clinical relevance of adhesion molecules and the potential for targeting these molecules for the amelioration of immune-mediated diseases.

Among the myriad receptors expressed by T cells, the sine qua non is the CD3/T cell receptor (CD3/TCR) complex, because it is uniquely capable of translating the presence of a specific antigen into intracellular signals necessary to trigger an immune response against a pathogen or tumor. Much work over the past 2 decades has attempted to define the signaling pathways leading from the CD3/TCR complex that culminate ultimately in the functions necessary for effective T cell immune responses, such as cytokine production. Here, we summarize recent advances in our understanding of the mechanisms by which the CD3/TCR complex controls integrin-mediated T cell adhesion, and discuss new information that suggests that there may be unexpected facets to this pathway that distinguish it from those previously defined.