Tags

Type your tag names separated by a space and hit enter

Control of Foxp3+ CD25+CD4+ regulatory cell activation and function by dendritic cells.
Int Immunol 2004; 16(12):1769-80II

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.

Authors+Show Affiliations

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.jpNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15520045

Citation

Fehérvári, Zoltán, and Shimon Sakaguchi. "Control of Foxp3+ CD25+CD4+ Regulatory Cell Activation and Function By Dendritic Cells." International Immunology, vol. 16, no. 12, 2004, pp. 1769-80.
Fehérvári Z, Sakaguchi S. Control of Foxp3+ CD25+CD4+ regulatory cell activation and function by dendritic cells. Int Immunol. 2004;16(12):1769-80.
Fehérvári, Z., & Sakaguchi, S. (2004). Control of Foxp3+ CD25+CD4+ regulatory cell activation and function by dendritic cells. International Immunology, 16(12), pp. 1769-80.
Fehérvári Z, Sakaguchi S. Control of Foxp3+ CD25+CD4+ Regulatory Cell Activation and Function By Dendritic Cells. Int Immunol. 2004;16(12):1769-80. PubMed PMID: 15520045.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Control of Foxp3+ CD25+CD4+ regulatory cell activation and function by dendritic cells. AU - Fehérvári,Zoltán, AU - Sakaguchi,Shimon, Y1 - 2004/11/01/ PY - 2004/11/3/pubmed PY - 2005/4/19/medline PY - 2004/11/3/entrez SP - 1769 EP - 80 JF - International immunology JO - Int. Immunol. VL - 16 IS - 12 N2 - 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. SN - 0953-8178 UR - https://www.unboundmedicine.com/medline/citation/15520045/Control_of_Foxp3+_CD25+CD4+_regulatory_cell_activation_and_function_by_dendritic_cells_ L2 - https://academic.oup.com/intimm/article-lookup/doi/10.1093/intimm/dxh178 DB - PRIME DP - Unbound Medicine ER -