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.
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.
Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Korea;
Hyo Jin
HJ
Park
Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Korea;
Joon Seok
JS
Park
Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Korea;
Yun Hee
YH
Jeong
Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Korea;
Jimin
J
Son
Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Korea;
Young Ho
YH
Ban
Division of Biological Resources Coordination, National Institute of Biological Resources, Environmental Research Complex, Incheon 404-170, Korea;
Byoung-Hee
BH
Lee
Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520;
Lieping
L
Chen
Division of Life and Pharmaceutical Sciences, Ewha Womans University, Seoul 120-750, Korea;
Jun
J
Chang
Department of Pathology, College of Medicine, Seoul National University, Seoul 110-799, Korea; and.
Doo Hyun
DH
Chung
Department of Microbiology and Immunology, Inje University College of Medicine, Busan 633-165, Korea.
Inhak
I
Choi
Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Korea; sjha@yonsei.ac.kr.
Sang-Jun
SJ
Ha
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D060890:B7-H1 Antigen / Q000235:genetics* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology; D002908:Chronic Disease; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D053450:Glucocorticoid-Induced TNFR-Related Protein / Q000378:metabolism; D056747:Immunomodulation; D016130:Immunophenotyping; D039001:Integrin alpha Chains / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D018655:Lymphocyte Count; D008212:Lymphocyte Depletion; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D061026:Programmed Cell Death 1 Receptor / Q000235:genetics* / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D014777:Virus Diseases / Q000235:genetics* / Q000276:immunology*
D015703:Antigens, CD; D060890:B7-H1 Antigen; D053450:Glucocorticoid-Induced TNFR-Related Protein; D039001:Integrin alpha Chains; D061026:Programmed Cell Death 1 Receptor; C091367:alpha E integrins