Structure and expression of murine CD30 and its role in cytokine production

M A Bowen1, R K Lee, G Miragliotta

  • 1Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, WA 98121, USA.

Insights

Murine CD30, a tumor necrosis factor receptor family member, is expressed on T cells and influences cytokine production. This research details its function and expression patterns in immune responses.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • CD30 is a member of the tumor necrosis factor receptor superfamily.
  • Understanding CD30's role in immune regulation is crucial for T cell biology.

Purpose of the Study:

  • To characterize murine CD30 (mCD30) and its function.
  • To investigate the expression patterns of mCD30 and its ligand in T cells.
  • To determine the signaling pathways activated by mCD30 stimulation.

Main Methods:

  • CDNA cloning and sequencing of murine CD30.
  • Production and functional analysis of soluble CD30-Ig fusion protein.
  • Generation of anti-mouse CD30 monoclonal antibodies (mAbs).
  • Analysis of CD30 and CD30 ligand mRNA expression in various tissues and activated T cells.
  • Cytokine production assays (IL-5, IFN-gamma) upon CD30 stimulation.

Main Results:

  • Murine CD30 cDNA encodes a 498-amino acid protein homologous to human CD30, with distinct extracellular domain features.
  • Soluble CD30-Ig fusion protein binds CD30 ligand and elicits anti-CD30 mAbs.
  • CD30 mRNA is highly expressed in thymus and activated spleen cells.
  • CD30 ligand peaks on CD4+ T cells early after activation, while CD30 peaks on CD8+ T cells later.
  • CD30 stimulation directly induces IL-5 production in CD30+ cytotoxic T lymphocyte (CTL) lines.

Conclusions:

  • Murine CD30 is a functional receptor with homology to human CD30.
  • CD30 and its ligand exhibit distinct temporal and cellular expression patterns during T cell activation.
  • CD30 signaling directly influences cytokine secretion, specifically IL-5, suggesting a pivotal role in T cell-mediated immune responses.