Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 39, Issue 5, Pages 1241-1251Publisher
WILEY
DOI: 10.1002/eji.200838913
Keywords
Apoptosis; CD4(+) T cells; Treg; ROS
Categories
Funding
- Korean Science and Engineering Foundation [R11-2002-098-08001-0]
- Korean government (MEST) [R0A-2008-000-20113-0]
- National Research Foundation of Korea [R0A-2008-000-20113-0, R11-2002-098-08001-0] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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Regulatory CD4(+) T cells are important for the homeostasis of immune cells, and their absence correlates with autoimmune disorders. However, how the immune system regulates Treg homeostasis remains unclear. We found that IFN-gamma-deficient-mice had more forkhead box P3 (FOXP3(+)) cells than WT mice in all secondary lymphoid organs except the thymus. However, T-bet- or IL-4R alpha-deficient mice did not show a similar increase. In vitro differentiation studies showed that conversion of naive T cells into FOXP3(+) cells (neo-generated inducible Treg (iTreg)) by TGF-beta was significantly inhibited by IFN-gamma in a STAT-1-dependent manner. Moreover, an in vivo adoptive transfer study showed that inhibition of FOXP3(+) iTreg generation by IFN-gamma was a T-cell autocrine effect. This inhibitory effect of IFN-gamma on iTreg generation was significantly abrogated after N-acetyl-L-cysteine treatment both in vitro and in vivo, indicating that IFN-gamma regulation of iTreg generation is dependent on ROS-mediated apoptosis. Therefore, our results suggest that autocrine IFN-gamma can negatively regulate the neo-generation of FOXP3(+) iTreg through ROS-mediated apoptosis in the periphery.
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