Title |
Cooperation of PD-1 and LAG-3 in the exhaustion of CD4+ and CD8+ T cells during bovine leukemia virus infection
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Published in |
Veterinary Research, June 2018
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DOI | 10.1186/s13567-018-0543-9 |
Pubmed ID | |
Authors |
Tomohiro Okagawa, Satoru Konnai, Asami Nishimori, Naoya Maekawa, Shinya Goto, Ryoyo Ikebuchi, Junko Kohara, Yasuhiko Suzuki, Shinji Yamada, Yukinari Kato, Shiro Murata, Kazuhiko Ohashi |
Abstract |
Bovine leukemia virus (BLV) is a retrovirus that infects B cells in cattle and causes bovine leukosis after a long latent period. Progressive exhaustion of T cell functions is considered to facilitate disease progression of BLV infection. Programmed death-1 (PD-1) and lymphocyte activation gene-3 (LAG-3) are immunoinhibitory receptors that contribute to T-cell exhaustion caused by BLV infection in cattle. However, it is unclear whether the cooperation of PD-1 and LAG-3 accelerates disease progression of BLV infection. In this study, multi-color flow cytometric analyses of PD-1- and LAG-3-expressing T cells were performed in BLV-infected cattle at different stages of the disease. The frequencies of PD-1+LAG-3+ heavily exhausted T cells among CD4+ and CD8+ T cells was higher in the blood of cattle with B-cell lymphoma over that of BLV-uninfected and BLV-infected cattle without lymphoma. In addition, blockade assays of peripheral blood mononuclear cells were performed to examine whether inhibition of the interactions between PD-1 and LAG-3 and their ligands by blocking antibodies could restore T-cell function during BLV infection. Single or dual blockade of the PD-1 and LAG-3 pathways reactivated the production of Th1 cytokines, interferon-γ and tumor necrosis factor-α, from BLV-specific T cells of the infected cattle. Taken together, these results indicate that PD-1 and LAG-3 cooperatively mediate the functional exhaustion of CD4+ and CD8+ T cells and are associated with the development of B-cell lymphoma in BLV-infected cattle. |
X Demographics
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United States | 1 | 50% |
Unknown | 1 | 50% |
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Type | Count | As % |
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Members of the public | 2 | 100% |
Mendeley readers
Geographical breakdown
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Unknown | 44 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Master | 8 | 18% |
Researcher | 6 | 14% |
Student > Ph. D. Student | 5 | 11% |
Student > Bachelor | 4 | 9% |
Other | 3 | 7% |
Other | 3 | 7% |
Unknown | 15 | 34% |
Readers by discipline | Count | As % |
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Agricultural and Biological Sciences | 9 | 20% |
Immunology and Microbiology | 9 | 20% |
Veterinary Science and Veterinary Medicine | 4 | 9% |
Medicine and Dentistry | 4 | 9% |
Mathematics | 1 | 2% |
Other | 2 | 5% |
Unknown | 15 | 34% |