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(Journal Article): Control of Foxp3+ CD25+CD4+ regulatory cell activation and function by dendritic cells.
Fehervari Z, Sakaguchi S (Department 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
)
IN:
Int Immunol
2004; 16(12):1769-1780
Impact Factor(s) of Int Immunol: 3.543 (2004), 3.69 (2003), 3.595 (2002), 3.611 (2001)
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ABSTRACT: Naturally occurring CD4+CD25+ regulatory T (TR) cells play crucial roles in normal immunohomeostasis. CD4+CD25+ TR cells exhibit a number of interesting in vitro properties including a 'default state' of profound anergy refractory to conventional T cell stimuli. We investigated the in vitro activation requirements of CD4+CD25+ TR cells using bone marrow-derived DC, which as professional antigen presenting cells (APC) can support the activation of normal naive T cells. Comparison of different APC types revealed that LPS-matured DC were by far the most effective at breaking CD4+CD25+ TR cell anergy and triggering proliferation, and importantly their IL-2 production. Examination of Foxp3, a key control gene for CD4+CD25+ TR cells, showed this to be stably expressed even during active proliferation. Although CD4+CD25+ TR cell proliferation was equivalent to that of CD25- cells their IL-2 production was considerably less. Use of IL-2-/- mice demonstrated that the DC stimulatory ability was not dependent on IL-2 production; nor did IL-15 appear crucial but was, at least in part, related to costimulation. DC also blocked normal CD4+CD25+ TR cell-mediated suppression partially via IL-6 secretion. DC therefore possess novel mechanisms to control the suppressive ability, expansion and/or differentiation of CD4+CD25+ TR cells in vivo.
TYPE OF PUBLICATION: Original article
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