Transient IFN-gamma 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-alpha/beta

Our previous studies have shown that UV-inactivated, nan-replicating herpes simplex virus type 1 (UV-HSV-1) triggers early and transient synthesis of IFN-alpha/beta 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 quant itative RT-PCR readout;assay, that IFN-gamma mRNA expression was rapidly an d transiently upregulated in draining lymph nodes when UV-HSV-1 was deliver ed in the ear dermis of C57BI/6 mice. An increased number of IFN-gamma-prod ucing cells was also detected in the lymph node by Row cytometric analysis. Two different subsets of cells, namely DX5(+) NK cells and CD3(epsilon)(+) T cells, accounted for this early IFN-gamma synthesis. Prompt upregulation of IFN-alpha and IL-12p40 mRNA was also recorded. We took advantage of IFN -alpha/beta-receptor knockout and wild-type 129 mice to study a potential r ole of IFN-alpha/beta in the signalling pathway leading to IFN-gamma, trans cription/translation. IFN-gamma mRNA upregulation still occurred in IFN-alp ha/beta-receptor(-/-) mice, showing that IFN-alpha/beta was dispensable. Th e use of IL-12-neutralizing antibodies, prior to UV-HSV-1 delivery, confirm ed the major role played by IL-12 in the early/transient IFN-gamma burst.