論文

国際誌
2011年9月26日

Increase of cells expressing PD-L1 in bovine leukemia virus infection and enhancement of anti-viral immune responses in vitro via PD-L1 blockade.

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

42
開始ページ
103
終了ページ
103
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1186/1297-9716-42-103

The inhibitory receptor programmed death-1 (PD-1) and its ligand, programmed death-ligand 1 (PD-L1) are involved in immune evasion mechanisms for several pathogens causing chronic infections. Blockade of the PD-1/PD-L1 pathway restores anti-virus immune responses, with concomitant reduction in viral load. In a previous report, we showed that, in bovine leukemia virus (BLV) infection, the expression of bovine PD-1 is closely associated with disease progression. However, the functions of bovine PD-L1 are still unknown. To investigate the role of PD-L1 in BLV infection, we identified the bovine PD-L1 gene, and examined PD-L1 expression in BLV-infected cattle in comparison with uninfected cattle. The deduced amino acid sequence of bovine PD-L1 shows high homology to the human and mouse PD-L1. The proportion of PD-L1 positive cells, especially among B cells, was upregulated in cattle with the late stage of the disease compared to cattle at the aleukemic infection stage or uninfected cattle. The proportion of PD-L1 positive cells correlated positively with prediction markers for the progression of the disease such as leukocyte number, virus load and virus titer whilst on the contrary, it inversely correlated with the degree of interferon-gamma expression. Blockade of the PD-1/PD-L1 pathway in vitro by PD-L1-specific antibody upregulated the production of interleukin-2 and interferon-gamma, and correspondingly, downregulated the BLV provirus load and the proportion of BLV-gp51 expressing cells. These data suggest that PD-L1 induces immunoinhibition in disease progressed cattle during chronic BLV infection. Therefore, PD-L1 would be a potential target for developing immunotherapies against BLV infection.

リンク情報
DOI
https://doi.org/10.1186/1297-9716-42-103
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/21943148
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3195098
ID情報
  • DOI : 10.1186/1297-9716-42-103
  • PubMed ID : 21943148
  • PubMed Central 記事ID : PMC3195098

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