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Clinical and Vaccine Immunology, June 2008, p. 954-962, Vol. 15, No. 6
1071-412X/08/$08.00+0     doi:10.1128/CVI.00428-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

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 {triangledown}

Viviana Marin-Esteban,1 Mubashira Abdul,1 Dominique Charron,1,2 Alain Haziot,1 and Nuala Mooney1,3*

Institut National de la Santé et de la Recherche Médicale U662, Paris, France,1 AP-HP, Hôpital Saint-Louis, Service d'Immunologie et d'Histocompatibilité,2 Université Paris Diderot Faculté de Médecine, Institut Universitaire d'Hématologie, Centre Hayem, Paris, France3

Received 24 October 2007/ Returned for modification 3 January 2008/ Accepted 30 March 2008

Monocyte-derived dendritic cells (DCs) differentiate in the presence of Toll-like-receptor (TLR) ligands in the course of ongoing infections. A single-stranded RNA (ssRNA) sequence, corresponding to the sequence of the U5 region of human immunodeficiency virus type 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 naive 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 interleukin 12p70 (IL-12p70) by ssRNA-DCs were selectively abrogated in response to a late TLR4, but not in response to a CD40, maturation signal. Inhibition of p38 mitogen-activated protein kinase 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 lipopolysaccharide, 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.

* Corresponding author. Mailing address: INSERM U662, Institut Universitaire d'Hématologie, Centre Hayem, Hôpital Saint-Louis, 1, Avenue Claude Vellefaux, 75010 Paris, France. Phone: (33) 1 42 49 95 51. Fax: (33) 1 42 49 46 41. E-mail: nuala.mooney{at}univ-paris-diderot.fr

{triangledown} Published ahead of print on 9 April 2008.

Clinical and Vaccine Immunology, June 2008, p. 954-962, Vol. 15, No. 6
1071-412X/08/$08.00+0     doi:10.1128/CVI.00428-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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