Lack of IFN-γ Production in Response to Antigenic Stimulation in Human IFN-τ-Treated Lymphocytes

Abstract

Interferon-τ (IFN-τ) is a type I IFN responsible for maternal recognition of the fetus in ruminants. In addition to its physiologic role, IFN-τ also inhibits HIV replication in human lymphocytes and macrophages and displays immunomodulatory effects but lacks the toxicity associated with other type I IFNs. Human IFN-α promotes a Th1 response, whereas IFN-τ has anti-inflammatory properties, inducing the production of Th2 cytokines in murine models of experimental autoimmune encephalitis (EAE) or fetal loss. We compared the effects of ovine IFN-τ (OvIFN-τ) and human IFN-α (HuIFN-α) on cytokine mRNA and protein production in human peripheral blood mononuclear cells (PBMCs) activated with a recall antigen, such as purified protein derivative (PPD) of tuberculin or with a proinflammatory stimulus, such as lipopolysaccharide (LPS). In both cases, IFN-α increased IFN-γ production, whereas IFN-τ did not and thereby promoted Th2 cytokine production. This original property renders IFN-τ a potential candidate for therapeutic applications in immune disorders, such as multiple sclerosis (MS), but its therapeutic use in the treatment of HIV infection should be considered with caution.