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Negative feedback regulation of T cells: Interleukin 2 and FOXP3 reciprocity
Author(s) -
Popmihajlov Zoran,
Smith Kendall A
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.848.22
Subject(s) - foxp3 , il 2 receptor , t cell receptor , cd8 , cd3 , microbiology and biotechnology , immune system , t cell , biology , immunology , chemistry
TCR activation of human T cells induces FOXP3 expression, but the mechanism remains unknown. We investigated the role of IL2 in the TCR/CD3‐induction of FOXP3 expression by normal human T cells in vitro. Freshly isolated PBM Cells were stimulated in vitro with anti‐CD3(OKT3) with or without anti‐CD25 and/or anti‐IL2 antibodies; human rIL2 was supplied exogenously. Four‐color flow cytometry was used to determine the expression of FOXP3. Anti‐CD3‐activation increased FOXP3 expression in both CD4+ and CD8+ T cells to a peak at 24h and by 96h was back to baseline levels. Both anti‐CD25 and anti‐IL2 caused a dose‐dependent inhibition of anti‐CD3‐stimulated FOXP3 expression, to a maximal suppression of 80% in CD4+ and >90% in CD8+ T cells, while the addition of rIL2 restored and prolonged FOXP3 expression. When anti‐CD3‐activated PBMCs were monitored daily for 4 days, FOXP3 and IL2 remained mutually exclusive, indicating that FOXP3 expression restricts but does not suppress IL2 expression upon TCR/CD3‐restimulation. TCR‐activated FOXP3 expression is primarily regulated by IL2/IL2R signaling and occurs only transiently in a subset of both CD4+ and CD8+ T cells. These results are consistent with an IL2‐dependent negative feedback loop that regulates the T cell immune response via FOXP3, so that FOXP3 cannot be considered solely a phenotypic marker for human T‐Reg cells. Supported by NIAID and the Belfer Foundation.