The role of lymphocyte function‐associated antigen 1 (LFA‐1) in the adherence of T lymphocytes to B lymphocytes

Mazerolles, Fabienne; Lumbroso, Catherine; Lecomte, Olivia; Deist, Françoise Le; Fischer, Alain

doi:10.1002/eji.1830180813

Cited by 49 publications

(22 citation statements)

References 37 publications

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“…Adhesion Assay-The adhesion assay or conjugate formation between T and B cells was performed as described previously (30). The HUT 78-CD4ϩ T cell line was incubated with hydroethidine (40 g/ml; Polysciences) for 20 min at 37°C, and B cells were incubated with sulfate fluorescein diacetate (100 g/ml; Molecular Probes) for 20 min at 37°C.…”

Section: Methodsmentioning

confidence: 99%

Molecular Events Associated with CD4-mediated Down-regulation of LFA-1-dependent Adhesion

Mazerolles¹,

Barbat²,

Trucy³

et al. 2002

Journal of Biological Chemistry

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We have previously shown that CD4 ligand binding inhibits LFA-1-dependent adhesion between CD4؉ T cells and B cells in a p56lck -and phosphatidylinositol 3-kinase (PI3-kinase)-dependent manner. In this work, downstream events associated with adhesion inhibition have been investigated. By using HUT78 T cell lines, CD4 ligands were shown to induce a dissociation of LFA-1 from cytohesin, a cytoplasmic protein known to bind LFA-1 and to enhance the affinity/avidity of LFA-1 for its ligand ICAM-1. A dissociation of PI3-kinase from cytohesin is also observed. In parallel, we have found that CD4 ligand binding induced a redistribution of PI3-kinase and of the tyrosine phosphatase SHP-2 to the membrane and induced a transient formation of protein interactions including PI3-kinase; an adaptor protein, Gab2; SHP-2; and a SH2 domain-containing inositol phosphatase, SHIP. By using antisense oligonucleotides or transfection of transdominant mutants, down-regulation of adhesion was shown to require the Gab2/PI3-kinase association and the expression of SHIP and SHP-2. We therefore propose that CD4 ligands, by inducing these molecular associations, lead to sustained local high levels of D-3 phospholipids and possibly regulate the cytohesin/LFA-1 association.Leukocyte adhesion is a fundamental process in leukocyte physiology, which is strictly regulated and involves a number of interactions between different adhesion proteins (1). As shown in blocking experiments with specific monoclonal Abs and transfection experiments (2), these adhesion processes are required for T cell activation and effector functions. We have previously shown that the LFA-1-dependent adhesion between CD4ϩ T cells (resting or T cell lines) and B cells was downregulated by CD4 ligands. This process requires the activities of the tyrosine kinase p56 lck associated with CD4 (3) and of phosphatidylinositol 3-kinase (PI3-kinase) 1 associated with the CD4⅐p56 lck complex (4). However, the molecular events and the relationship between these kinases required for the down-regulation induced by CD4 binding and the modification of the affinity/avidity of LFA-1 are not clearly understood.PI3-kinase is an intracellular enzyme mainly consisting of two subunits: the p110 catalytic subunit (␣ and ␤ isoforms) and the p85 regulatory subunit (␣ and ␤ isoforms) (5, 6). This enzyme phosphorylates the D-3 position of the inositol ring of phosphatidylinositol (PI), phosphatidylinositol 4-phosphate (PI 4-P), and phosphatidylinositol 4,5-bisphosphate (PI 4,5-P 2 ) (7). These phospholipids are one of the intermediary messengers for the CD4-mediated down-regulation of LFA-1-dependent adhesion since inhibitors of PI3-kinase activity abrogate the regulatory event (8). The mechanism by which PI3-kinase upon CD4 ligand binding mediates down-regulation of LFA-1 adhesion is unknown. PI3-kinase can exert an opposite effect: Kolanus et al. (9) have recently shown that the D-3 phospholipids synthesized by PI3-kinase increase the affinity of LFA-1 for its ligand ICAM-1 by a modification of as...

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Section: Methodsmentioning

confidence: 99%

Molecular Events Associated with CD4-mediated Down-regulation of LFA-1-dependent Adhesion

Mazerolles¹,

Barbat²,

Trucy³

et al. 2002

Journal of Biological Chemistry

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“…The rotenone-sensitive NADH oxidase activities, the antimycin-sensitive succinate oxidase activities, and the KCN-sensitive cytochrome c oxidase activities were measured after disruption of20 X 106 lymphocytes (-20°C, overnight) in the presence of specific substrates (0.32 mM NADH, 10 mM succinate, or 50 mM reduced cytochrome c) and inhibitors as described (4,5). EBV-transformed cell lines were submitted to B cell line cloning as described (8,9). …”

Section: Biochemical and Histopathological Investigationsmentioning

confidence: 99%

Pearson's marrow-pancreas syndrome. A multisystem mitochondrial disorder in infancy.

Rötig¹,

Cormier²,

Blanche³

et al. 1990

J. Clin. Invest.

422

174

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“…Two adhesion events that are of particular interest are the interaction between ICAM-I (CD54) and C D l l d C D 1 8 complex, and between CD2 and leukocyte function-associated antigen 3 (LFA-3) (CD58), not only because of their demonstrated role in cell-to-cell adhesion (17)(18)(19), but also because of their ability to facilitate antigen presentation to T lymphocytes and cytolysis (20)(21)(22)(23). Therefore, w e used a quantitative in vitro cellular adhesion system t o examine the relative contributions of ICAM-1-CD1 ldCD18 and of CD2-LFA-3 to T lymphocyte adhesion to cytokine-activated human synovial fibroblasts.…”

Section: T Lymphocyte Adhesion To Human Synovial Fibroblastsmentioning

confidence: 99%

T Lymphocyte Adhesion to Human Synovial Fibroblasts. Role of Cytokines and the Interaction Between Intercellular Adhesion Molecule 1 and CD11a/CD18

Krzesicki

Fleming

Winterrowd

et al. 1991

Arthritis & Rheumatism

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We studied the adhesion of human peripheral blood T lymphocytes to human synovial fibroblasts stimulated with interferon-y (IFNy), tumor necrosis factor a (TNFcu), interleukin-lp (IL-lp), or combinations of these cytokines. T lymphocytes bound poorly to untreated human synovial fibroblasts. IFN y treatment resulted id the largest increase in adhesion, followed by TNFa and IL-1p. Combinations of IFNy + TNFa and IFNy + I L -l p had a synergistic effect on intercellular adhesion molecule 1 (ICAM-1) expression and adhesion. The increase in cellular adhesion induced by cytokines correlated with the up-regulation of the number of cells expressing ICAM-1 and the density of antigedcell. There was no synergistic effect on leukocyte functionassociated antigen 3 (LFA-3) or on HLA class I or class I1 antigen expression. Adhesion was only partially inhibited by anti-ICAM-1, anti-LFA-1, or anti-CD18. These findings suggest the existence of ICAM-1-independent and CDll/CDlS-independent adhesion mechanisms. Anti-LFA-3 was completely ineffective as an inhibitor of adhesion. There was no additive or synergistic advantage of using combinations of antibod-~

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The role of lymphocyte function‐associated antigen 1 (LFA‐1) in the adherence of T lymphocytes to B lymphocytes

Cited by 49 publications

References 37 publications

Molecular Events Associated with CD4-mediated Down-regulation of LFA-1-dependent Adhesion

Molecular Events Associated with CD4-mediated Down-regulation of LFA-1-dependent Adhesion

Pearson's marrow-pancreas syndrome. A multisystem mitochondrial disorder in infancy.

T Lymphocyte Adhesion to Human Synovial Fibroblasts. Role of Cytokines and the Interaction Between Intercellular Adhesion Molecule 1 and CD11a/CD18

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