Upregulation of interleukin-4 and IFN-gamma expression by IFN-tau, a member of the type I IFN family

Trophoblast interferon-tau (IFN-tau) is a new member of the type I IFN fami ly that is produced in large quantities by the ruminant conceptus. Like oth er type I IFN, IFN-tau inhibits viral replication and activates natural kil ler (NK)-mediated cytotoxicity. In mice and humans, type I IFN enhances typ e I T helper (Th) cell responses, but the effects of type I IFN, including IFN-tau, on cytokine expression by bovine Th cells have not been described. The present study determined the effects of IFN-tau on interleukin-4 (IL-4 ), IFN-gamma, and IL-10 expression by antigen-specific, CD4(+) T cell lines derived from cattle immune to either Babesia bovis, Babesia bigemina rhopt ry-associated protein-1, or Anaplasma marginale. IFN-tau upregulated IFN-ga mma secretion and steady-state levels of IFN-gamma and IL-4 mRNA by cell li nes cultured for 3-6 weeks. In contrast, the steady-state levels of IL-10 m RNA were either not changed or inhibited at these times. Similar effects we re obtained with human IFN-alpha. Comparison of the quantities of IFN-gamma , IL-4, and IL-10 transcripts in IFN-tau-treated or IFN-alpha-treated cultu res revealed that even though IFN-gamma was the predominant cytokine expres sed by all T cell lines, both IFN-gamma and IL-4 steady-state transcript le vels were upregulated by a comparable degree. Thus, these studies demonstra te that IFN-tau is an immunomodulatory cytokine that promotes enhanced IL-4 and IFN-gamma responses by effector T cells but not, strictly speaking, Th 1-biased responses in cattle. These results indicate the potential use of t his cytokine as an adjuvant in ruminants to boost cell-mediated immune resp onses.