Increased bovine Tim-3 and its ligand expressions during bovine leukemia virus infection
<p>Abstract</p> <p>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 ro...
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doaj-4d62ad33ca1347a8a4499e4a1f1546402020-11-25T00:33:43ZengBMCVeterinary Research0928-42491297-97162012-05-014314510.1186/1297-9716-43-45Increased bovine Tim-3 and its ligand expressions during bovine leukemia virus infectionOkagawa TomohiroKonnai SatoruIkebuchi RyoyoSuzuki SaoriShirai TatsuyaSunden YujiOnuma MisaoMurata ShiroOhashi Kazuhiko<p>Abstract</p> <p>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<sup>+</sup> and CD8<sup>+</sup> cells, while Gal-9 mRNA is mainly expressed in monocyte and T cells. Tim-3 mRNA expression in CD4<sup>+</sup> and CD8<sup>+</sup> 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.</p> http://www.veterinaryresearch.org/content/43/1/45 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Okagawa Tomohiro Konnai Satoru Ikebuchi Ryoyo Suzuki Saori Shirai Tatsuya Sunden Yuji Onuma Misao Murata Shiro Ohashi Kazuhiko |
spellingShingle |
Okagawa Tomohiro Konnai Satoru Ikebuchi Ryoyo Suzuki Saori Shirai Tatsuya Sunden Yuji Onuma Misao Murata Shiro Ohashi Kazuhiko Increased bovine Tim-3 and its ligand expressions during bovine leukemia virus infection Veterinary Research |
author_facet |
Okagawa Tomohiro Konnai Satoru Ikebuchi Ryoyo Suzuki Saori Shirai Tatsuya Sunden Yuji Onuma Misao Murata Shiro Ohashi Kazuhiko |
author_sort |
Okagawa Tomohiro |
title |
Increased bovine Tim-3 and its ligand expressions during bovine leukemia virus infection |
title_short |
Increased bovine Tim-3 and its ligand expressions during bovine leukemia virus infection |
title_full |
Increased bovine Tim-3 and its ligand expressions during bovine leukemia virus infection |
title_fullStr |
Increased bovine Tim-3 and its ligand expressions during bovine leukemia virus infection |
title_full_unstemmed |
Increased bovine Tim-3 and its ligand expressions during bovine leukemia virus infection |
title_sort |
increased bovine tim-3 and its ligand expressions during bovine leukemia virus infection |
publisher |
BMC |
series |
Veterinary Research |
issn |
0928-4249 1297-9716 |
publishDate |
2012-05-01 |
description |
<p>Abstract</p> <p>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<sup>+</sup> and CD8<sup>+</sup> cells, while Gal-9 mRNA is mainly expressed in monocyte and T cells. Tim-3 mRNA expression in CD4<sup>+</sup> and CD8<sup>+</sup> 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.</p> |
url |
http://www.veterinaryresearch.org/content/43/1/45 |
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