Tyrosine kinase activity associated with the CD7 antigen: correlation with regulation of T cell integrin function

Abstract

Rapid up-regulation of the functional activity of integrin adhesion receptors is a hallmark of T cell activation. Monoclonal antibody engagement of the CD7 antigen on human T cells results in an increase in beta 1 and beta 2 integrin-mediated adhesion within minutes. This suggests that CD7 is capable of transducing intracellular signals, and is consistent with other indirect studies implicating CD7 as a signaling receptor on T cells. In this report, we have explored the intracellular mechanism by which CD7 modulates integrin functional activity. First, CD7-mediated up-regulation of T cell adhesion was found to be unique when compared to phorbol ester stimulation and CD3/T cell receptor cross-linking, based on differences in the kinetics of activation-dependent integrin-mediated adhesion and lack of increase in CD2 functional activity. Second, up-regulation of integrin activity mediated by CD7 cross-linking was completely inhibited by the tyrosine kinase inhibitor herbimycin A. Third, antiphosphotyrosine immunoblotting demonstrated that antibody engagement of CD7 results in a rapid but transient increase in tyrosine phosphorylation in human T cells. Finally, CD7 immunoprecipitates contain in vitro kinase activity, as demonstrated by phosphorylation of a predominant band of 80 kDa and multiple other bands. Phosphoamino acid analysis of the 80-kDa substrate revealed phosphorylation on tyrosine as well as serine and threonine residues. Together, our results suggest that CD7 is associated with tyrosine kinase activity and that this tyrosine kinase activity correlates with the ability of CD7 to regulate T cell integrin functional activity.

Identification of a novel, human multilymphoid progenitor in cord blood

“…Although its exact function is unknown, cross-linking of CD7 results in tyrosine kinase-mediated up-regulation of ␤1 and ␤2 integrin expression on T 35 and NK cells, 36 thus modulating adhesion to fibronectin. 37 The ligand for CD7 has not been identified, although a recent report suggested that galectin-1 induced apoptosis in T cells may involve binding to CD7.…”

Cutting Edge: CD7 Delivers a Pro-Apoptotic Signal During Galectin-1-Induced T Cell Death

“…CD7 ϩ T cells may bind galectin-1 expressed by stromal or dendritic cells in tissues where T cells die, such as the thymus during T cell development (19,21) or peripheral lymphoid organs following an immune response (4,20). Galectin-1 may mediate interactions between T cells and stromal cells directly (1,2,8), or galectin-1 may modulate T cell adhesion by cross-linking CD7 on T cells, thereby up-regulating integrin-mediated adhesion (22,23). We have previously demonstrated that 3 Abbreviation used in this paper: [Ca 2ϩ ] i , intracellular calcium concentration.…”

T Cell Signal Transduction and the Role of CD7 in Costimulation

“…This effect on adhesion was reduced by treatment with either staurosporine or dibutyryl cAMP, suggesting a role for PKC and cAMP, respectively, in CD7-induced adhesion (142). Further studies have shown that the induction of increased integrin adhesion by CD7 ligation is abolished by pretreatment of the cells with herbimycin A, a tyrosine kinase inhibitor (150). A role for the lipid kinase PI3K in CD7 signaling has been suggested by the observation that the PI3K inhibitors Wortmannin and LY294002 or a dominant negative form of PI3K inhibited CD7-induced integrin adhesion (147).…”

“…This multimeric complex was shown to contain tyrosine kinase activity (144). Independently, CD7 immunoprecipitated from purified CD4 + human T cells was shown to associate with a tyrosine kinase activity (150); the tyrosine phosphorylated band in these immunoprecipitates had a relative molecular weight of 80 kDa, but remains unidentified (150).…”