1. PD-1 Upregulated on Regulatory T Cells during Chronic Virus Infection Enhances the Suppression of CD8+ T Cell Immune Response via the Interaction with PD-L1 Expressed on CD8+ T Cells
- Author
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Yun Hee Jeong, Inhak Choi, Jimin Son, Hyojin Park, Joon Seok Park, Byoung Hee Lee, Doo Hyun Chung, Young Ho Ban, Jun Chang, Sang Jun Ha, and Lieping Chen
- Subjects
T cell ,Programmed Cell Death 1 Receptor ,Immunology ,Gene Expression ,chemical and pharmacologic phenomena ,Cell Communication ,CD8-Positive T-Lymphocytes ,Lymphocyte Activation ,T-Lymphocytes, Regulatory ,B7-H1 Antigen ,Lymphocyte Depletion ,Immunophenotyping ,Immunomodulation ,Mice ,Interleukin 21 ,Antigens, CD ,T-Lymphocyte Subsets ,Glucocorticoid-Induced TNFR-Related Protein ,medicine ,Animals ,Immunology and Allergy ,Cytotoxic T cell ,Lymphocyte Count ,IL-2 receptor ,Antigen-presenting cell ,Mice, Knockout ,business.industry ,ZAP70 ,hemic and immune systems ,Natural killer T cell ,Disease Models, Animal ,Phenotype ,medicine.anatomical_structure ,Virus Diseases ,Chronic Disease ,Female ,business ,Integrin alpha Chains ,CD8 - Abstract
Regulatory T (Treg) cells act as terminators of T cell immuniy during acute phase of viral infection; however, their role and suppressive mechanism in chronic viral infection are not completely understood. In this study, we compared the phenotype and function of Treg cells during acute or chronic infection with lymphocytic choriomeningitis virus. Chronic infection, unlike acute infection, led to a large expansion of Treg cells and their upregulation of programmed death-1 (PD-1). Treg cells from chronically infected mice (chronic Treg cells) displayed greater suppressive capacity for inhibiting both CD8+ and CD4+ T cell proliferation and subsequent cytokine production than those from naive or acutely infected mice. A contact between Treg and CD8+ T cells was necessary for the potent suppression of CD8+ T cell immune response. More importantly, the suppression required cell-specific expression and interaction of PD-1 on chronic Treg cells and PD-1 ligand on CD8+ T cells. Our study defines PD-1 upregulated on Treg cells and its interaction with PD-1 ligand on effector T cells as one cause for the potent T cell suppression and proposes the role of PD-1 on Treg cells, in addition to that on exhausted T cells, during chronic viral infection.
- Published
- 2015