Lack of IFN-gamma production in response to antigenic stimulation in human IFN-tau-treated lymphocytes.
Interferon-tau (IFN-tau) is a type I IFN responsible for maternal recognition of the fetus in ruminants. In addition to its physiologic role, IFN-tau 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-alpha promotes a Th1 response, whereas IFN-tau 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-tau (OvIFN-tau) and human IFN-alpha (HuIFN-alpha) 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-alpha increased IFN-gamma production, whereas IFN-tau did not and thereby promoted Th2 cytokine production. This original property renders IFN-tau 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.
Rogez-Kreuz
Christine
C
Service de Neurovirologie, CEA, CRSSA, Université Paris XI, EPHE, IPSC, Fontenay-aux-Roses, France.
Manéglier
Benjamin
B
Dereuddre-Bosquet
Nathalie
N
Dormont
Dominique
D
Clayette
Pascal
P
D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics; D006801:Humans; D007370:Interferon Type I / Q000276:immunology / Q000494:pharmacology*; D016898:Interferon-alpha / Q000494:pharmacology; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D011257:Pregnancy Proteins / Q000276:immunology / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D016207:Cytokines; D007370:Interferon Type I; D016898:Interferon-alpha; D008070:Lipopolysaccharides; D011257:Pregnancy Proteins; D012333:RNA, Messenger; C020947:interferon tau; D007371:Interferon-gamma