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

Authors:
Smith EL, Finney HM, Nesbitt AM, Ramsdell F, Robinson MK
In:
Source: Immunology
Publication Date: (2006)
Issue: 119(2): 203-11
Research Area:
Immunotherapy / Hematology
Cells used in publication:
T cell, human peripheral blood unstim.
Species: human
Tissue Origin: blood
T cell, human stim.
Species: human
Tissue Origin: blood
Platform:
Nucleofector™ I/II/2b
Abstract
SFOXP3 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.