Crosslinking of the T cell-specific accessory molecules CD7 and CD28 modulates T cell adhesion.

Abstract

SummaryRegulated adhesion enables T cells to migrate through tissue and transiently interact with an endless succession of cells. Monoclonal antibody (mAb) engagement of the CD3/T cell receptor (TCR) complex results in a rapid and transient augmentation of the adhesion function of LFA-1 and VLA integrin molecules on human T cells. We show in this study that mAb crosslinking of the T cell-specific accessory molecules CD7 and CD28, or treatment with the Ca 2+ ionophore A23187, results in the rapid induction of integrin-mediated adhesion to three distinct ligands: the extracellular matrix protein fibronectin, and the cell surface molecules ICAM-1 and VCAM-1. Like CD3 crosslinking, increased adhesion via CD7 and CD28 crosslinking appears to involve both protein kinase C (PKC) and cAMP-dependent protein kinases. In contrast, A23187 induction of adhesion is unaffected by PKC inhibitors. CD7 is preferentially expressed on naive T cells and is unique in being a potent inducer of naive T cell adhesion. Enhanced expression/function of adhesion-inducing molecules thus overcomes relative deficits in adhesion receptor expression."[ mphocytes express a multitude of cell surface receptors .1_r that are capable of mediating adhesion to other cells and proteins (1, 2). Regulation of the functional activity of these adhesion molecules is critical to both T cell migration and recognition, since T cells must transiently interact with cells and proteins found in the extracellular environment. One important element in the regulation of adhesion is the rapid increase in the adhesive function of integrin molecules that occurs after crosslinking of the CD3/TCR complex by mAb (3-6) or foreign antigen (7). Integrins mediate T cell adhesion to other cells via interactions such as LFA-1 binding to its ligands ICAM-1 and ICAM-2, and VLA-4 binding to VCAM-1, and also to extraceUular matrix (ECM) 1 components via interactions such as VLA-4 and VLA-5 to fibronectin (FN) (1, 2, 8). Activation of other lymphoid cell types by mAb crosslinking of functionally relevant cell surface molecules also results in increased LFA-l-dependent adhesion. Such molecules include HLA class II (9) and CD14 (10) on monocytes, and surface immunoglobulin (11), CD19 (12), and CD40 (13) We reasoned that the functional activity of integrin molecules on human T cells might also be increased by mAb crosslinking of other molecules besides the CD3/TCR. In this study we report the ability of three different activation signals to increase integrin-mediated adhesion: the Ca 2 + ionophore A23187, and mAb crosslinking of the CD7 and CD28 molecules, both of which have been implicated as T cell activation molecules (14-16). These activation signals can coordinately increase T cell adhesion to three different ligands: the LFA-1 ligand ICAM-1, the VLA-4 endothelial cell surface ligand VCAM-1, and the VLA-4 and VLA-5 ligand FN. We demonstrate similarities in the biochemical signals generated by CD3, CDT, and CD28 crosslinking that distinguish receptor-mediated activation from the eff...

β1 Integrin-dependent binding of Jurkat cells to fibronectin is regulated by a serine-threonine phosphatase

“…These findings would seem to indicate a co-regulation of ␤ 1 and ␤ 2 integrins through serine-threonine phosphatases. Further evidence for coregulation comes from studies on T cells where activation by cross-linking of CD3, CD7, or CD28 was shown to activate both VLA-4 and LFA-1 [13]. Moreover, CD3 stimulation induces colocalization of both VLA-4 and LFA-1 to F-actin [30].…”

“…In addition to the amount of expression of cell surface adhesion molecules, the functional state of integrins can be regulated, leading to changes in the affinity for counterligand binding without affecting the level of cell surface expression [11]. Changes in T cell integrin activity can be induced in vitro by a variety of stimulating agents, such as phorbol esters, calcium ionophore, and cross-linking of T cell receptors like CD2, CD3, CD7, and CD28 [3,[12][13][14]. Furthermore, the activation state of integrins can be altered by antibodies against ␤ 1 integrins, like 8A2, that bind to the receptor and induce a more active form [15] or by alterations of the extracellular cation milieu, both of which appear to affect the conformation of the integrin binding site [16,17].…”

Expression and function of beta1 integrins on human eosinophils

“…Furthermore, cell-surface receptors, called integrin regulators, can induce an inside-out signal. These integrin regulators include the TCR complex, CD2, CD28, CD7 (Chan et al 1991, Shimizu et al 1992) and cell surface signaling proteins of the transmembrane-4 superfamily that include CD9, CD53, CD63, CD82 and CD81 (Mannion et al 1996).…”

Separation of integrin-dependent adhesion from morphological changes based on differential PLC specificities

“…Ligation of the T cell receptor (TCR), CD2, CD7, and CD28 receptors have all been shown to up-regulate integrin adhesion in a wortmannin-sensitive manner, indicating a requirement for PI 3-K [4][5][6]9]. With regard to outside-in signaling, it has been shown that HPB-ALL T leukemia cells adhere to immobilized fibronectin (FN) through the integrin ␣ 4 ␤ 1 and that this interaction activates phospholipase A 2 (PLA 2 ) to produce arachidonic acid (AA) followed by the formation of cellular pseudopodia [10].…”

“…Leukocyte integrins are normally maintained in a low-affinity conformation and require an up-regulatory signal to form a strong interaction with their specific substrates. Phosphoinositide 3-kinase (PI 3-K) and protein kinase C (PKC) [2][3][4][5][6][7][8] have been implicated as mediators of this cascade, referred to as inside-out signaling [1]. Once activated, the ligand-bound integrin receptor then initiates the production of intracellular signals in the form of classic biochemical messengers and nonclassic mechanical signals.…”