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Transient IFN- synthesis in the lymph node draining a dermal site loaded with UV-irradiated herpes simplex virus type 1: an NK- and CD3-dependent process regulated by IL-12 but not by IFN-/

Unité de Virologie et Immunologie Moléculaires, Institut National de la Recherche Agronomique, F-78352 Jouy-en-Josas cedex, France¹
Unité d’Immunophysiologie et Parasitisme Intracellulaire, Institut Pasteur, Paris, France²

Author for correspondence: Sabine Riffault. Fax +33 1 34 65 26 21. e-mail riffault{at}biotec.jouy.inra.fr

Our previous studies have shown that UV-inactivated, non-replicating herpes simplex virus type 1 (UV-HSV-1) triggers early and transient synthesis of IFN-/ in the mouse regional lymph node when delivered upstream (i.e. in the ear dermis). In this study, it is demonstrated, by use of a quantitative RT–PCR readout assay, that IFN- mRNA expression was rapidly and transiently upregulated in draining lymph nodes when UV-HSV-1 was delivered in the ear dermis of C57Bl/6 mice. An increased number of IFN--producing cells was also detected in the lymph node by flow cytometric analysis. Two different subsets of cells, namely DX5⁺ NK cells and CD3⁺ T cells, accounted for this early IFN- synthesis. Prompt upregulation of IFN- and IL-12p40 mRNA was also recorded. We took advantage of IFN-/-receptor knockout and wild-type 129 mice to study a potential role of IFN-/ in the signalling pathway leading to IFN- transcription/translation. IFN- mRNA upregulation still occurred in IFN-/-receptor^-/- mice, showing that IFN-/ was dispensable. The use of IL-12-neutralizing antibodies, prior to UV-HSV-1 delivery, confirmed the major role played by IL-12 in the early/transient IFN- burst.

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