THE INTERFERON-ALPHA BETA RESPONSES OF MICE TO HERPES-SIMPLEX VIRUS STUDIED AT THE BLOOD AND TISSUE-LEVEL IN-VITRO AND IN-VIVO/

Murine mononuclear leucocytes from bone marrow, spleen, lymph node and blood stimulated in vitro by UV-irradiated Herpes simplex type I viru s (HSV) produced about equal proportions of IFN-alpha and -beta determ ined by immunoassay. Thymocytes produced only IFN-alpha. The frequency of IFN-alpha/beta mRNA containing cells detected by in situ hybridiza tion was highest with bone marrow (15 per 10(4) cells), followed by sp leen (4/10(4)), lymph node (2/10(4)), blood (1/10(4)) and thymus (0.2/ 10(4)). Such IFN-alpha/beta producing cells (IPCs) were heavily labell ed in autoradiographs, each producing about 0.4 U of IFN. After one in travenous injection of UV-irradiated HSV in mice, high levels of IFN-a lpha and -beta were present in blood at 3-9 h and little or none at 24 h or later. Frequent cells strongly positive for IFN-alpha mRNA at in situ hybridization and for IFN-alpha/beta at immunohistochemical stai ning were found almost exclusively in the marginal zones of spleens. O ccasional IPCs were detected in lymph nodes but not in bone marrow, li ver and kidneys. The marginal zone IPCs may be the major source of IFN in blood, and high splenic levels of IFN-alpha/beta should have effic ient antiviral and immunoregulatory functions.