T cell aggregation induced through CD43: intracellular signals and inhibition by the immunomodulatory drug leflunomide

J Leukoc Biol. 2003 Dec;74(6):1083-93. doi: 10.1189/jlb.0303095. Epub 2003 Sep 12.

Abstract

The CD43 coreceptor molecule has been shown to participate in lymphocyte adhesion and activation. Leukocyte homotypic aggregation results from a cascade of intracellular signals delivered to the cells upon engagement of different cell-surface molecules with their natural ligands. This phenomenon requires an active metabolism, reorganization of the cytoskeleton, and relocalization of cell-surface molecules. The aim of this study was to identify some of the key members of the signaling cascade leading to T lymphocyte homotypic aggregation following CD43 engagement. CD43-mediated homotypic aggregation of T lymphocytes required the participation of Src kinases, phospholipase C-gamma2, protein kinase C, phosphatidylinositol-3 kinase, as well as extracellular-regulated kinase 1/2 and p38. Data shown here suggest that these signaling molecules play a central role in regulating actin cytoskeleton remodeling after CD43 ligation. We also evaluated the ability of immunomodulatory drugs such as leflunomide to block the CD43-mediated homotypic aggregation. Leflunomide blocked the recruitment of targets of the Src family kinases as well as actin polymerization, diminishing the ability of T lymphocytes to aggregate in response to CD43-specific signals, suggesting that this drug might control the migration and recruitment of lymphoid cells to inflamed tissues.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Antigens, CD*
  • Cell Aggregation
  • Enzyme Precursors / metabolism
  • Humans
  • Immunosuppressive Agents / pharmacology*
  • Intracellular Signaling Peptides and Proteins
  • Isoxazoles / pharmacology*
  • Jurkat Cells
  • Leflunomide
  • Leukosialin
  • Lymphocyte Activation
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phospholipase C gamma
  • Protein Kinase C / metabolism
  • Protein-Tyrosine Kinases / metabolism
  • Sialoglycoproteins / metabolism*
  • Signal Transduction / drug effects*
  • Syk Kinase
  • T-Lymphocytes / metabolism*
  • Type C Phospholipases / metabolism
  • p38 Mitogen-Activated Protein Kinases
  • src-Family Kinases / metabolism

Substances

  • Actins
  • Antigens, CD
  • Enzyme Precursors
  • Immunosuppressive Agents
  • Intracellular Signaling Peptides and Proteins
  • Isoxazoles
  • Leukosialin
  • SPN protein, human
  • Sialoglycoproteins
  • Protein-Tyrosine Kinases
  • SYK protein, human
  • Syk Kinase
  • src-Family Kinases
  • Protein Kinase C
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • Type C Phospholipases
  • Phospholipase C gamma
  • Leflunomide