Increased bovine Tim-3 and its ligand expressions during bovine leukemia virus infection.

Abstract

The immunoinhibitory receptor T cell immunoglobulin domain and mucin domain-3 (Tim-3) and its ligand, galectin-9 (Gal-9), are involved in the immune evasion mechanisms for several pathogens causing chronic infections. However, there is no report concerning the role of Tim-3 in diseases of domestic animals. In this study, cDNA encoding for bovine Tim-3 and Gal-9 were cloned and sequenced, and their expression and role in immune reactivation were analyzed in bovine leukemia virus (BLV)-infected cattle. Predicted amino acid sequences of Tim-3 and Gal-9 shared high homologies with human and mouse homologues. Functional domains, including tyrosine kinase phosphorylation motif in the intracellular domain of Tim-3 were highly conserved among cattle and other species. Quantitative real-time PCR analysis showed that bovine Tim-3 mRNA is mainly expressed in T cells such as CD4+ and CD8+ cells, while Gal-9 mRNA is mainly expressed in monocyte and T cells. Tim-3 mRNA expression in CD4+ and CD8+ cells was upregulated during disease progression of BLV infection. Interestingly, expression levels for Tim-3 and Gal-9 correlated positively with viral load in infected cattle. Furthermore, Tim-3 expression level closely correlated with up-regulation of IL-10 in infected cattle. The expression of IFN-γ and IL-2 mRNA was upregulated when PBMC from BLV-infected cattle were cultured with Cos-7 cells expressing Tim-3 to inhibit the Tim-3/Gal-9 pathway. Moreover, combined blockade of the Tim-3/Gal-9 and PD-1/PD-L1 pathways significantly promoted IFN-γ mRNA expression compared with blockade of the PD-1/PD-L1 pathway alone. These results suggest that Tim-3 is involved in the suppression of T cell function during BLV infection.

• Authors: Tomohiro Okagawa, Satoru Konnai, Ryoyo Ikebuchi, Saori Suzuki, Tatsuya Shirai, Yuji Sunden, Misao Onuma, Shiro Murata, Kazuhiko Ohashi
• Journal: Veterinary research (Vet Res) Vol. 43 Pg. 45 (May 23 2012) ISSN: 1297-9716 [Electronic] England
• PMID: 22621175 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA, Complementary
• Galectins
• Membrane Proteins
• RNA, Messenger

Topics

• Amino Acid Sequence
• Animals
• Cattle
• Cattle Diseases (genetics, metabolism, virology)
• Cloning, Molecular
• DNA, Complementary (genetics, metabolism)
• Enzootic Bovine Leukosis (genetics, metabolism, virology)
• Galectins (genetics, metabolism)
• Gene Expression Regulation
• Leukemia Virus, Bovine (physiology)
• Membrane Proteins (genetics, metabolism)
• Molecular Sequence Data
• Phylogeny
• RNA, Messenger (genetics, metabolism)
• Viral Load (veterinary)