Splice variants of human FOXP3 are functional inhibitors of human CD4+ T-cell activation.
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.
Smith
Emma L
EL
UCB-Celltech., Slough, UK. Emma.Smith@UCB-group.com
Finney
Helene M
HM
Nesbitt
Andrew M
AM
Ramsdell
Fred
F
Robinson
Martyn K
MK
D001483:Base Sequence; D018106:CD28 Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D003001:Cloning, Molecular; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics* / Q000276:immunology; D008969:Molecular Sequence Data; D020033:Protein Isoforms / Q000235:genetics / Q000276:immunology; D022821:RNA Splice Sites / Q000235:genetics*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D016415:Sequence Alignment; D014162:Transfection
D018106:CD28 Antigens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D020033:Protein Isoforms; D022821:RNA Splice Sites; D011948:Receptors, Antigen, T-Cell