RT Journal Article
SR Electronic
T1 Murine CD4<sup>+</sup>CD25<sup>+</sup> Regulatory T Cells Fail to Undergo Chromatin Remodeling Across the Proximal Promoter Region of the IL-2 Gene
JF The Journal of Immunology
JO J. Immunol.
FD American Association of Immunologists
SP 4994
OP 5001
DO 10.4049/jimmunol.173.8.4994
VO 173
IS 8
A1 Su, Leon
A1 Creusot, Remi J.
A1 Gallo, Elena M.
A1 Chan, Steven M.
A1 Utz, Paul J.
A1 Fathman, C. Garrison
A1 Ermann, Joerg
YR 2004
UL http://www.jimmunol.org/content/173/8/4994.abstract
AB CD4+CD25+ regulatory T cells (Treg) acquire unique immunosuppressive properties while maintaining an anergy phenotype when activated in vitro under conditions that induce IL-2 production and proliferation in conventional CD4+ T cells. We investigated the mechanism underlying one component of this naturally anergic phenotype, the inability of the Treg cells to produce IL-2 following activation. Analysis of freshly isolated murine CD4+CD25+ Treg and conventional CD4+CD25− T cells following PMA/ionomycin stimulation demonstrated no differences in inducible AP-1 formation, an important transcriptional complex in regulating IL-2 gene expression. Although p38 MAPK and ERK1/2 protein kinases were phosphorylated with similar kinetics, we observed diminished activation of JNK in the CD4+CD25+ Treg cells. However, lentiviral-mediated reconstitution of the JNK pathway using a constitutively active construct did not overcome the block in IL-2 synthesis. Using a PCR-based chromatin accessibility assay we found that the minimal IL-2 promoter region of CD4+CD25+ Treg cells, unlike conventional CD4 T cells, did not undergo chromatin remodeling following stimulation, suggesting that the inability of CD4+CD25+ Treg cells to secrete IL-2 following activation is controlled at the chromatin level.