ACTIVATION OF INTERFERON-INDUCIBLE GENES IN MICE BY POLY RI-RC OR ALLOANTIGENS

We have examined the effects of synthetic dsRNA (poly rI:rC) treatment or of immunization with irradiated allogeneic cells on the expression in vivo of several interferon (IFN)-inducible genes. For this purpose, DBA/2 mice were injected i.p. once with poly rI:rC, or once and then again 3 weeks later, with irradiated C3H/He spleen cells and the effect of these treatments on the levels of the following mRNAs was determined: 202, 2',5'-oligoadenylate synthetase (2-5A synthetase), class I and class II major histocompatibility antigens, and beta-actin. After poly rI:rC treatment, the levels of the 202 and 2-5A synthetase mRNAs in the spleen and in the bone marrow peaked between 12 and 24 h and decreased thereafter. The class I mRNA levels started to increase at 12 h, peaked at 24 h, and declined thereafter. No increase in class II mRNA expression was observed after poly rI:rC injection, whereas beta-actin levels remained unchanged. Pretreatment of DBA/2 mice with sheep anti-murine IFN-alpha/beta antibodies before poly rI:rC injection strongly diminished the induction of 202 mRNA, indicating that IFN-alpha/beta mediated this induction. When irradiated C3H/He spleen cells were injected into DBA/2 mice, the class I and class II mRNAs in the spleen, but not in the bone marrow, started to increase at 12 h, peaked between 48 and 96 h, and decreased thereafter. No increase in the levels of 202 and 2-5A synthetase mRNAs was detected, whereas beta-actin levels remained unchanged. Pretreatment of DBA/2 mice with rat monoclonal anti-murine IFN-gamma antibodies before allogeneic cell injection significantly decreased class II mRNA levels in the spleen, suggesting the involvement of IFN-gamma in this induction. The above studies conducted in vivo (a) reveal differences in the tissue and gene specificity of gene activation between dsRNA and allogeneic cells and (b) indicate that gene activation by dsRNA is mediated at least in part by IFN-alpha/beta, whereas gene activation by allogeneic cells is mediated at least in part by IFN-gamma.