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Control of Foxp3+ CD25+CD4+ regulatory cell activation and function by dendritic cells
Zoltán Fehérvári1, Shimon Sakaguchi
1Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Shogo-in 53, Sakyo-ku, Kyoto 606-8507, Japan. zed72@frontier.kyoto-u.ac.jp
International Immunology
|November 3, 2004
Summary
Regulatory T (TR) cells are vital for immune balance but are typically anergic. Lipopolysaccharide-matured dendritic cells (DC) effectively activate TR cells, breaking their anergy and promoting proliferation.
Area of Science:
- Immunology
- Cell Biology
Background:
- CD4+CD25+ regulatory T (TR) cells are essential for maintaining immunohomeostasis.
- TR cells exhibit an anergic state, resisting conventional T cell activation stimuli in vitro.
Purpose of the Study:
- To investigate the in vitro activation requirements of CD4+CD25+ TR cells.
- To determine the role of dendritic cells (DC) in overcoming TR cell anergy and controlling their function.
Main Methods:
- Utilized bone marrow-derived dendritic cells (DC) as antigen-presenting cells (APC) to activate CD4+CD25+ TR cells.
- Compared different APC types, focusing on LPS-matured DC.
- Analyzed Foxp3 expression, IL-2 and IL-15 production, and costimulatory molecule involvement.
- Investigated DC-mediated suppression of TR cell activity, including IL-6 secretion.
Main Results:
- LPS-matured DC were highly effective in breaking CD4+CD25+ TR cell anergy, inducing proliferation and IL-2 production.
- Foxp3 expression remained stable during active TR cell proliferation.
- TR cell proliferation was comparable to CD25- cells, but IL-2 production was lower.
- DC's stimulatory capacity was independent of IL-2 and IL-15, suggesting a role for costimulation.
- DC partially blocked TR cell-mediated suppression through IL-6 secretion.
Conclusions:
- Dendritic cells possess unique mechanisms to activate and control CD4+CD25+ regulatory T cells.
- DC can overcome TR cell anergy, promote their expansion, and modulate their suppressive functions in vivo.