CD40 ligation releases immature dendritic cells from the control of regulatory CD4+CD25+ T cells.
We report that disruption of CD154 in nonobese diabetic (NOD) mice abrogates the helper function of CD4+CD25- T cells without impairing the regulatory activity of CD4+CD25+ T cells. Whereas CD4+ T cells from NOD mice enhanced a diabetogenic CD8+ T cell response in monoclonal TCR-transgenic NOD mice, CD4+ T cells from NOD.CD154(-/-) mice actively suppressed it. Suppression was mediated by regulatory CD4+CD25+ T cells capable of inhibiting CD8+ T cell responses induced by peptide-pulsed dendritic cells (DCs), but not peptide/MHC monomers. It involved inhibition of DC maturation, did not occur in the presence of CD154+ T-helper cells, and could be inhibited by activation of DCs with LPS, CpG DNA, or an agonistic anti-CD40 mAb. Thus, in at least some genetic backgrounds, CD154-CD40 interactions and innate stimuli release immature DCs from suppression by CD4+CD25+ T cells.
Serra
Pau
P
Julia McFarlane Diabetes Research Centre, University of Calgary, Faculty of Medicine, 3330 Hospital Drive NW, Calgary, Alberta, Canada T2N 4N1.
Amrani
Abdelaziz
A
Yamanouchi
Jun
J
Han
Bingye
B
Thiessen
Shari
S
Utsugi
Toshihiro
T
Verdaguer
Joan
J
Santamaria
Pere
P
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D019013:CD40 Antigens / Q000378:metabolism*; D023201:CD40 Ligand / Q000235:genetics / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D018899:CpG Islands / Q000502:physiology; D003713:Dendritic Cells / Q000378:metabolism*; D003920:Diabetes Mellitus / Q000209:etiology / Q000378:metabolism; D008264:Macrophages; D051379:Mice; D015375:Receptors, Interleukin-2 / Q000378:metabolism*
D019013:CD40 Antigens; D015375:Receptors, Interleukin-2; D023201:CD40 Ligand