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Scott N. Mueller, Vijay K. Vanguri, Sang-Jun Ha, Erin E. West, Mary E. Keir, Jonathan N. Glickman, Arlene H. Sharpe, Rafi Ahmed
J Clin Invest. 2010;
120(7):2508
doi:10.1172/JCI40040
Abstract |
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T
he inhibitory receptor programmed death 1 (PD-1) is upregulated on antigen-specific CD8+ T cells during persistent viral infections. Interaction with PD-1 ligand 1 (PD-L1) contributes to functional exhaustion of responding T cells and may limit immunopathology during infection. PD-L1 is expressed on both hematopoietic and nonhematopoietic cells in tissues. However, the exact roles of PD-L1 on hematopoietic versus nonhematopoietic cells in modulating immune responses are unclear. Here we used bone marrow chimeric mice to examine the effects of PD-L1 deficiency in hematopoietic or nonhematopoietic cells during lymphocytic choriomeningitis virus clone 13 (LCMV CL-13) infection. We found that PD-L1 expression on hematopoietic cells inhibited CD8+ T cell numbers and function after LCMV CL-13 infection. In contrast, PD-L1 expression on nonhematopoietic cells limited viral clearance and immunopathology in infected tissues. Together, these data demonstrate that there are distinct roles for PD-L1 on hematopoietic and nonhematopoietic cells in regulating CD8+ T cell responses and viral clearance during chronic viral infection.
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(7)
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Cell Proliferation
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Glia
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Yan Luan, Jianqi Ju, Liqun Luo, Zheng Zhang, Jun Wang, Dan-Ming Zhu, Liang Cheng, Shu-Ye Zhang, Lieping Chen, Fu-Sheng Wang, Shengdian Wang
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Journal of Viral Hepatitis
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PD-L1 blockade overrides Salmonella typhimurium-mediated diabetes prevention in NOD mice: No role for Tregs
Stephen A. Newland, Jenny M. Phillips, Pietro Mastroeni, Miyuki Azuma, Paola Zaccone, Anne Cooke
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Eur. J. Immunol.
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2011 |
The PDL1-PD1 Axis Converts Human TH1 Cells into Regulatory T Cells
S. Amarnath, C. W. Mangus, J. C. M. Wang, F. Wei, A. He, V. Kapoor, J. E. Foley, P. R. Massey, T. C. Felizardo, J. L. Riley
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Science Translational Medicine
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2011 |
Nonhematopoietic antigen blocks memory programming of alloreactive CD8+ T cells and drives their eventual exhaustion in mouse models of bone marrow transplantation
Barry Flutter, Noha Edwards, Farnaz Fallah-Arani, Stephen Henderson, Jian-Guo Chai, Shivajanani Sivakumaran, Sara Ghorashian, Clare L. Bennett, Gordon J. Freeman, Megan Sykes, Ronjon Chakraverty
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J. Clin. Invest.
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2010 |
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