Dendritic cells differentiated in the presence of a single stranded viral RNA sequence conserve their ability to activate CD4 T lymphocytes but lose their capacity for Th1 polarization

Institut National de la Santé et de la Recherche Médicale U662, Paris, France; AP-HP, Hôpital St Louis, Service d'Immunologie et d'Histocompatibilité, Paris, France; and Université Paris Diderot Faculté de Médecine, Institut Universitaire d'Hématologie, Centre Hayem, Paris, France

^* To whom correspondence should be addressed. Email: nuala.mooney{at}univ-paris-diderot.fr.

	Abstract

Monocyte-derived dendritic cells (DC) differentiate in the presence of Toll-like-receptor (TLR) ligands in the course of ongoing infections. A single–stranded RNA sequence, corresponding to the sequence of the U5 region of HIV-1 RNA, was used to mimic viral activation of TLR7 in human DCs. We determined the effector potential of DCs differentiated in the presence of this ssRNA molecule (ssRNA-DCs). ssRNA-DCs phenotypically resembled mature DCs. In contrast, their capacity to allostimulate naïve CD4+T cells resembled that of conventional immature DCs and could be increased by TLR4 stimulation. Th1 polarization of CD4+ T cells and production of IL-12p70 by ssRNA-DCs was selectively abrogated in response to a late TLR4 but not in response to a CD40 maturation signal. Inhibition of p38MAPK partially restored IL-12p70 secretion but did not restore Th1 polarization whereas addition of exogenous IL-12 led to recovery of Th1 polarization. In contrast to LPS, ssRNA induced IL-12p70 production at the very earliest stages of DC differentiation indicating a particular role for TLR7 in monocyte-derived DCs recently engaged in differentiation. These data demonstrate generation of phenotypically mature DCs with the ability to expand CD4+ T lymphocytes lacking Th1/2-polarizing capacity.