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 family that is produced in large quantities by the ruminant conceptus. Like other type I IFN, IFN-tau inhibits viral replication and activates natural killer (NK)-mediated cytotoxicity. In mice and humans, type I IFN enhances type 1 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 rhoptry-associated protein-1, or Anaplasma marginale. IFN-tau upregulated IFN-gamma secretion and steady-state levels of IFN-gamma and IL-4 mRNA by cell lines cultured for 3-6 weeks. In contrast, the steady-state levels of IL-10 mRNA were either not changed or inhibited at these times. Similar effects were 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 cultures revealed that even though IFN-gamma was the predominant cytokine expressed by all T cell lines, both IFN-gamma and IL-4 steady-state transcript levels were upregulated by a comparable degree. Thus, these studies demonstrate that IFN-tau is an immunomodulatory cytokine that promotes enhanced IL-4 and IFN-gamma responses by effector T cells but not, strictly speaking, Thl-biased responses in cattle. These results indicate the potential use of this cytokine as an adjuvant in ruminants to boost cell-mediated immune responses.
Tuo
W
W
Department of Veterinary Pathology and Microbiology, Washington State University, Pullman 99164, USA.
MacMillan
H
H
Günter
N
N
Bazer
F W
FW
Brown
W C
WC
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002417:Cattle; D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects; D007370:Interferon Type I / Q000494:pharmacology*; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics; D015847:Interleukin-4 / Q000096:biosynthesis*; D011257:Pregnancy Proteins / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation
D000998:Antiviral Agents; D007370:Interferon Type I; D011257:Pregnancy Proteins; C020947:interferon tau; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma