Differential control of T regulatory cell proliferation and suppressive activity by mature plasmacytoid versus conventional spleen dendritic cells.
Anergy and suppression are cardinal features of CD4(+)CD25(+)Foxp3(+) T cells (T regulatory cells (Treg)) which have been shown to be tightly controlled by the maturation state of dendritic cells (DC). However, whether lymphoid organ DC subsets exhibit different capacities to control Treg is unclear. In this study, we have analyzed, in the rat, the role of splenic CD4(+) and CD4(-) conventional DC and plasmacytoid DC (pDC) in allogeneic Treg proliferation and suppression in vitro. As expected, in the absence of exogenous IL-2, Treg did not expand in response to immature DC. Upon TLR-induced maturation, all DC became potent stimulators of CD4(+)CD25(-) T cells, whereas only TLR7- or TLR9-matured pDC induced strong proliferation of CD4(+)CD25(+)Foxp3(+) T cells in the absence of exogenous IL-2. This capacity of pDC to reverse Treg anergy required cell contact and was partially CD86 dependent and IL-2 independent. In suppression assays, Treg strongly suppressed proliferation and IL-2 and IFN-gamma production by CD4(+)CD25(-) T cells induced by mature CD4(+) and CD4(-) DC. In contrast, upon stimulation by mature pDC, proliferating Treg suppressed IL-2 production by CD25(-) cells but not their proliferation or IFN-gamma production. Taken together, these results suggest that anergy and the suppressive function of Treg are differentially controlled by DC subsets.
Ouabed
Asmahan
A
INSERM Unite 643, Centre Hospitalier Universitaire de Nantes, Institut de Transplantation et de Recherche en Transplantation-Urologie-Néphrologie, Université de Nantes, 30 boulevard Jean Monnet, Nantes, France.
Hubert
Francois-Xavier
FX
Chabannes
Dominique
D
Gautreau
Laetitia
L
Heslan
Michèle
M
Josien
Régis
R
D000818:Animals; D051940:B7-2 Antigen / Q000276:immunology; D049109:Cell Proliferation; D017635:Clonal Anergy / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology / Q000494:pharmacology; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D010950:Plasma Cells / Q000166:cytology / Q000276:immunology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000166:cytology / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*; D051199:Toll-Like Receptor 7 / Q000276:immunology; D051217:Toll-Like Receptor 9 / Q000276:immunology
D051940:B7-2 Antigen; C497966:Cd86 protein, rat; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; C489639:TLR7 protein, rat; C489640:Tlr9 protein, rat; D051199:Toll-Like Receptor 7; D051217:Toll-Like Receptor 9; D007371:Interferon-gamma