Superantigen stimulation reveals the contribution of Lck to negative regulation of T cell activation

J Immunol. 2004 Jan 1;172(1):222-30. doi: 10.4049/jimmunol.172.1.222.

Abstract

The conventional paradigm of T cell activation through the TCR states that Lck plays a critical activating role in this signaling process. However, the T cell response to bacterial superantigens does not require Lck. In this study we report that not only is Lck dispensable for T cell activation by superantigens, but it actively inhibits this signaling pathway. Disruption of Lck function, either by repression of Lck gene expression or by selective pharmacologic inhibitors of Lck, led to increased IL-2 production in response to superantigen stimulation. This negative regulatory effect of Lck on superantigen-induced T cell responses required the kinase activity of Lck and correlated with early TCR signaling, but was independent of immunological synapse formation and TCR internalization. Our data demonstrate that the multistage role of Lck in T cell signaling includes the activation of a negative regulatory pathway of T cell activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Cell Line, Transformed
  • Cytokines / biosynthesis
  • DNA-Binding Proteins / metabolism
  • Down-Regulation / drug effects
  • Down-Regulation / genetics
  • Down-Regulation / immunology*
  • Enterotoxins / immunology*
  • Humans
  • Jurkat Cells
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / genetics
  • Lymphocyte Activation / immunology*
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / antagonists & inhibitors
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / biosynthesis
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / genetics
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / physiology*
  • Membrane Proteins / physiology
  • NFATC Transcription Factors
  • Nuclear Proteins*
  • Pyrimidines / pharmacology
  • Receptors, Antigen, T-Cell / physiology
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Signal Transduction / immunology
  • Staphylococcus aureus / immunology
  • Superantigens / immunology*
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / enzymology*
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / microbiology
  • Transcription Factors / metabolism

Substances

  • AG 1879
  • Cytokines
  • DNA-Binding Proteins
  • Enterotoxins
  • Membrane Proteins
  • NFATC Transcription Factors
  • Nuclear Proteins
  • Pyrimidines
  • Receptors, Antigen, T-Cell
  • Superantigens
  • Transcription Factors
  • antigen T cell receptor, zeta chain
  • enterotoxin E, Staphylococcal
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck)