Splice variants of human FOXP3 are functional inhibitors of human CD4+ T-cell activation

Immunology. 2006 Oct;119(2):203-11. doi: 10.1111/j.1365-2567.2006.02425.x.


FOXP3 has been identified as a key regulator of immune homeostasis. Mutations within the FOXP3 gene result in dysregulated CD4+ T-cell function and elevated cytokine production, leading to lymphoproliferative disease. FOXP3 expression in CD4+ T cells is primarily detected with the CD4+ CD25+ regulatory T-cell population. In humans the protein is detected as a doublet following immunoblot analysis. The lower band of the doublet has been identified as a splice isoform lacking a region corresponding to exon 2. The aim of this study was to investigate whether the splice variant form lacking exon 2 and a new novel splice variant lacking both exons 2 and 7, were functional inhibitors of CD4+ T-cell activation. The data generated showed that full-length FOXP3 and both splice variant forms of the protein were functional repressors of CD4+ T-cell activation.

MeSH terms

  • Base Sequence
  • CD28 Antigens / immunology
  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Proliferation
  • Cells, Cultured
  • Cloning, Molecular
  • Forkhead Transcription Factors / genetics*
  • Forkhead Transcription Factors / immunology
  • Forkhead Transcription Factors / metabolism
  • Humans
  • Immune Tolerance / genetics
  • Immune Tolerance / immunology
  • Lymphocyte Activation / genetics*
  • Lymphocyte Activation / immunology
  • Molecular Sequence Data
  • Protein Isoforms / genetics
  • Protein Isoforms / immunology
  • RNA Splice Sites / genetics*
  • Receptors, Antigen, T-Cell / immunology
  • Sequence Alignment
  • Transfection


  • CD28 Antigens
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Protein Isoforms
  • RNA Splice Sites
  • Receptors, Antigen, T-Cell