HERPES-SIMPLEX VIRUS INDUCES APPEARANCE OF INTERFERON-ALPHA BETA-PRODUCING CELLS AND PARTIALLY INTERFERON-ALPHA/BETA-DEPENDENT ACCUMULATIONOF LEUKOCYTES IN MURINE REGIONAL LYMPH-NODES/

An in vivo experimental system involving the local induction of interf eron-alpha/beta (IFN-alpha/beta) responses was established in mice by injecting s.c. ultraviolet (UV)-inactivated herpes simplex virus (HSV) in the right ears, the left ears receiving phosphate-buffered saline (PBS) as a control, Circulating IFN-alpha/beta was present in blood as early as 6 h postinjection, and little or none was found 24 h postinj ection, Identification of IFN-alpha/beta-producing cells, carried out by immunohistochemistry and in situ hybridization, demonstrated that t he IFN response occurred mainly in the lymph node draining the HSV-inj ected ear and not in the contralateral lymph node, Occasionally, IFN-a lpha/beta-producing cells were found in the spleen and in the skin, Th e injected HSV caused an inflammatory reaction in the skin and an almo st threefold enlargement of the draining lymph node within 6 h, The la tter was characterized by a general accumulation of all major lymphocy te subsets and a striking infiltration of neutrophils. Injection s.c. of neutralizing anti-IFN-alpha/beta antibodies before HSV injection re duced the increase in size of the draining lymph node by approximately 50% at 6 h, and no significant effects were seen at 24 h, The localiz ation of cells producing IFN-alpha/beta in the lymph node and the capa city of such IFN-alpha/beta to at least partially mediate an early acc umulation of cells suggest that the local IFN-alpha/beta response may have an important role in the initiation of early antiviral immune res ponses.