Lack of IFN-γγ Production in Response to Antigenic Stimulation in Human IFN-ττ-Treated Lymphocytes
AbstractInterferon-ττ (IFN-ττ) is a type I IFN responsible for maternal recognition of the fetus in ruminants. In addition to its physiologic role, IFN-ττ 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-αα promotes a Th1 response, whereas IFN-ττ 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-ττ (OvIFN-ττ) and human IFN-αα (HuIFN-αα) 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-αα increased IFN-γγ production, whereas IFN-ττ did not and thereby promoted Th2 cytokine production. This original property renders IFN-ττ 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.