Transient IFN-γ 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-α/β
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-α/β 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-γ 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-γ-producing cells was also detected in the lymph node by flow cytometric analysis. Two different subsets of cells, namely DX5+ NK cells and CD3ϵ+ T cells, accounted for this early IFN-γ synthesis. Prompt upregulation of IFN-α and IL-12p40 mRNA was also recorded. We took advantage of IFN-α/β-receptor knockout and wild-type 129 mice to study a potential role of IFN-α/β in the signalling pathway leading to IFN-γ transcription/translation. IFN-γ mRNA upregulation still occurred in IFN-α/β-receptor−/− mice, showing that IFN-α/β 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-γ burst.
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Transient IFN-γ 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-α/β