Plasmacytoid dendritic cells prime IL-10-producing T regulatory cells by inducible costimulator ligand.
Although there is evidence for distinct roles of myeloid dendritic cells (DCs [mDCs]) and plasmacytoid pre-DCs (pDCs) in regulating T cell-mediated adaptive immunity, the concept of functional DC subsets has been questioned because of the lack of a molecular mechanism to explain these differences. In this study, we provide direct evidence that maturing mDCs and pDCs express different sets of molecules for T cell priming. Although both maturing mDCs and pDCs upregulate the expression of CD80 and CD86, only pDCs upregulate the expression of inducible costimulator ligand (ICOS-L) and maintain high expression levels upon differentiation into mature DCs. High ICOS-L expression endows maturing pDCs with the ability to induce the differentiation of naive CD4 T cells to produce interleukin-10 (IL-10) but not the T helper (Th)2 cytokines IL-4, -5, and -13. These IL-10-producing T cells are T regulatory cells, and their generation by ICOS-L is independent of pDC-driven Th1 and Th2 differentiation, although, in the later condition, some contribution from endogenous IL-4 cannot be completely ruled out. Thus, in contrast to mDCs, pDCs are poised to express ICOS-L upon maturation, which leads to the generation of IL-10-producing T regulatory cells. Our findings demonstrate that mDC and pDCs are intrinsically different in the expression of costimulatory molecules that drive distinct types of T cell responses.
Ito
Tomoki
T
Department of Immunology, M.D. Anderson Cancer Center, Graduate School of Biomedical Sciences at Houston, The University of Texas, Houston, TX 77030, USA.
Yang
Maria
M
Wang
Yui-Hsi
YH
Lande
Roberto
R
Gregorio
Josh
J
Perng
Olivia A
OA
Qin
Xiao-Feng
XF
Liu
Yong-Jun
YJ
Gilliet
Michel
M
D000328:Adult; D015703:Antigens, CD; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000145:classification / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D060945:Inducible T-Cell Co-Stimulator Ligand; D016753:Interleukin-10 / Q000096:biosynthesis*; D022423:Myeloid Cells / Q000145:classification / Q000276:immunology / Q000378:metabolism; D010950:Plasma Cells / Q000145:classification / Q000276:immunology / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology; D015854:Up-Regulation
D015703:Antigens, CD; C498514:ICOSLG protein, human; D060945:Inducible T-Cell Co-Stimulator Ligand; D011506:Proteins; D016753:Interleukin-10