論文

国際誌
2012年5月23日

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

Veterinary research
  • Tomohiro Okagawa
  • ,
  • Satoru Konnai
  • ,
  • Ryoyo Ikebuchi
  • ,
  • Saori Suzuki
  • ,
  • Tatsuya Shirai
  • ,
  • Yuji Sunden
  • ,
  • Misao Onuma
  • ,
  • Shiro Murata
  • ,
  • Kazuhiko Ohashi

43
開始ページ
45
終了ページ
45
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1186/1297-9716-43-45

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.

リンク情報
DOI
https://doi.org/10.1186/1297-9716-43-45
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/22621175
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3443419
ID情報
  • DOI : 10.1186/1297-9716-43-45
  • PubMed ID : 22621175
  • PubMed Central 記事ID : PMC3443419

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