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[[Beta].sub.2] integrin molecules are involved in a multitude of cellular events, including adhesion, migration, and cellular activation. Here, we studied the influence of [[Beta].sub.2] integrins on interleukin-2 (IL-2)-mediated signal transduction in human CD[4.sup.+] T cell lines obtained from healthy donors and a leukocyte adhesion deficiency (LAD) patient. We show that IL-2 induces tyrosine phosphorylation of a 125-kDa protein and homotypic adhesion in [[Beta].sub.2] integrin (CD18)-positive but not in [[Beta].sub.2]-integrin-negative T cells. EDTA, an inhibitor of integrin adhesion, blocks IL-2-induced tyrosine phosphorylation of the 125-kDa protein but not other proteins in [[Beta].sub.2]-integrin-positive T cells. Likewise, a [[Beta].sub.2] integrin (CD18) antibody selectively inhibits induction of the 125-kDa phosphotyrosine protein, whereas cytokine-mediated tyrosine phosphorylation of other proteins is largely unaffected. Immunoprecipitation experiments indicate that the IL-2-induced 125-kDa phosphotyrosine protein is the focal adhesion kinase-related protein B (fakB). Thus, IL-2 induces strong tyrosine phosphorylation of fakB in [[Beta].sub.2]-integrin-positive but not in [[Beta].sub.2]-integrin-negative T cells, and CD18 mAb selectively blocks IL-2-induced fakB-tyrosine phosphorylation in [[Beta].sub.2]-integrin-positive T cells. In parallel experiments, IL-2 does not induce or augment tyrosine phosphorylation of [p125.sup.FAK]. In conclusion, our data indicate that IL-2 induces [[Beta].sub.2]-integrin-dependent signal transduction events involving the tyrosine kinase substrate fakB.

Phosphoamino acid analysis and Western immunoblotting techniques help identify a focal adhesion kinase (FAK)-related tyrosine kinase substrate, fak B, which undergoes tyrosine phosphorylation with lymphocyte antigen receptor stimulation in human B and T cells. The protein combines with T cell antigen receptor (TCR/CD3)-associated tyrosine kinase 2Ap-70 in the T cells to form stable complexes. The regulation of fak B is distant from that of its putative homologue PP125 FAK. fak B mediates an antigen-induced lymphocyte signaling.

LFA-1 is linked to the tyrosine kinase signaling pathway that induces tyrosine phosphorylation and activation of phospholipase C-gamma1 (PLC-gamma 1). Integrin beta-chain (CD18) crosslinking freely stimulated downstream mobility of intracellular Ca2+ and strongly induced T-cell antigen receptor (TCR)-induced Ca2+ flux with an increase in amplitude and kinetics. Beta2-integrin signaling through this path was totally inhibited by herbimycin A and was prevented by TCR modulation. Tyrosine phosphorylation of an 80-kDa protein substrate was enhanced after CD18 crosslinking, but it was not TCR-dependent.

The B-cell adhesion molecule CD22 is involved in the stimulation of T-cells, which is also dependent on CD45. The nature of the CD22-mediated T-cell stimulation was further characterized by examining the effects of CD22 on the early events of T-cell signaling. The results showed that CD22 interacts directly with several isoforms of CD45. It is proposed that CD45 plays an active role in transducing CD22-mediated T-cell responses.

The signal modulation of protein-tyrosine kinase activity induced by CD3 and CD4 were reduced by thiol-specific oxidation in T-cells. CD3 and CD4-induced Ca2+ responses in T cells were inhibited by N-ethylmaleimide which was correlated with diminished level of phospholipase Cgamma1 (PLCgamma1) tyrosine phosphorylation. The active state of an immunopurified enzyme from N-ethylmaleimide-treated cells indicated the non-direct effect of PLCgamma1 catalytic activity. Overall results indicated the existence of a process involving neutrophile regulation of T-lymphocyte activation responses.

CD5 is a transmembrane protein that is expressed on the surface of T cells and a subset of B cells. The absence of CD5 rendered thymocytes hyperresponsive to stimulation through the T cell antigen receptor (TCR) in vitro. Selection of T cells expressing three distinct transgenic TCRs was also abnormal in CD5-deficient mice. These observations indicate that CD5 can influence the fate of developing thymocytes by acting as a negative regulator of TCR-mediated signal transduction., Signal transduction through the TCR determines the outcome of thymic selection (1). The T lymphocyte transmembrane protein CD5 is part of a receptor complex that also comprises the TCR-CD3 θ [...]