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Blood, 15 September 2004, Vol. 104, No. 6, pp. 1596-1597.
Plasmacytoid dendritic cell: vive le dilettante!WASHINGTON UNIVERSITY SCHOOL OF MEDICINE
Whether plasmacytoid dendritic cells (pDCs) are effective in presenting antigens has been a matter of debate. Schlecht and colleagues provide evidence that pDCs can indeed prime CD8 T cells specific for viral antigens.
In this issue of Blood, Schlecht and colleagues address these issues using an original and clever approach that involves activating pDCs with different stimuli in vivo, recovering activated pDCs, loading them with antigen in vitro, and adoptively transferring them into mice. Remarkably, pDCs injected intravenously home efficiently to the spleen, making it possible to study their ability to stimulate or inhibit naive and memory T-cell responses. The results of these experiments demonstrate that the antigen-presenting capacity of pDCs is critically dependent on their state of activation and, in particular, the stimuli used to activate them in vivo. Two types of stimuli were evaluated: a cytosine-guanine (CpG) oligonucleotide, which activates pDCs through toll-like receptor (TLR) 9, and heat-inactivated influenza virus, which stimulates pDCs through TLR7. The pDCs activated with CpG can stimulate memory CD8 T cells but not naive CD8 T cells. In contrast, pDCs activated with influenza virus can prime naive CD8 T cells, although less efficiently than DCs. Moreover, T-cell responses primed by pDCs can be recalled by a second antigenic challenge as efficiently as those primed by classical DCs. Finally, immature pDCs pulsed with a peptide antigen induce neither antigen-specific CD8 T-cell responses nor tolerance to subsequent challenge with the same peptide.
That antigen presentation is induced by influenza virus but not CpG is surprising, as both stimuli activate the same TLR/myeloid differentiation factor 88 (MyD88) signaling pathway. How can this be? One clue to this difference can be found in one of the earliest experiments performed by Schlecht and colleagues, showing that influenza virus triggers IFN-
Related Article in Blood Online:
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| Copyright © 2004 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
and IFN-
) when exposed to DNA and RNA viruses. The ability of pDCs to stimulate T cells and secrete type I IFN has raised 3 fundamental questions. (1) Do pDCs present antigens as effectively as classical DCs? While it is generally agreed that pDCs are less efficient than DCs, whether pDCs can prime naive T cells, as DCs do, or just expand memory T cells, as B cells do, remains a matter of debate. (2) Does activation of pDCs affect the quality of antigen-specific T-cell responses? While activated pDCs up-regulate T-cell stimulatory molecules, it has been proposed that immature pDCs may in fact induce regulatory T cells that actively suppress antigen-specific T-cell responses. (3) Does pDC secretion of type I IFN contribute directly or indirectly to antigen presentation?