The Journal of Experimental Medicine
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Published online January 2, 2007
doi:10.1084/jem.20061660
The Journal of Experimental Medicine, Vol. 204, No. 1, 105-115
The Rockefeller University Press, 0022-1007 $30.00
© 2007 Ito et al.
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ARTICLE

 Plasmacytoid dendritic cells prime IL-10–producing T regulatory cells by inducible costimulator ligand

Tomoki Ito1, Maria Yang1, Yui-Hsi Wang1, Roberto Lande1, Josh Gregorio1,2, Olivia A Perng1, Xiao-Feng Qin1,2, Yong-Jun Liu1,2, and Michel Gilliet1,2

1 Department of Immunology, M.D. Anderson Cancer Center, and 2 Graduate School of Biomedical Sciences at Houston, The University of Texas, Houston, TX 77030

CORRESPONDENCE Michel Gilliet: mgilliet{at}mdanderson.org

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.

Abbreviations used: CD40L, CD40 ligand; ICOS, inducible costimulator; ICOS-L, ICOS ligand; mDC, myeloid DC; pDC, plasmacytoid pre-DC; Th, T helper; TLR, Toll-like receptor.


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