Dendritic Cell PD-L1 Limits Autoimmunity and Follicular T Cell Differentiation and Function.
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Abstract | The programmed death (PD)-1 coinhibitory receptor regulates the balance between T cell activation and tolerance. Although the PD-1 ligands, PD-L1 and PD-L2, are expressed on a variety of cell types, the cell type-specific functions of PD-1 ligands in inducing signals through PD-1 are unknown. In this study, we use PD-L1 conditional knockout mice to investigate the cell type-specific functions of PD-L1. We demonstrate that PD-L1 expressed on dendritic cells (DCs), and to a lesser extent on B cells, attenuates the progression of experimental autoimmune encephalomyelitis and inhibits naive and effector T cells. PD-1 is highly expressed on effector populations, including T follicular helper (Tfh) cells and T follicular regulatory (Tfr) cells, which reside in germinal centers. We also show that DC PD-L1 is essential for limiting Tfh and Tfr cell differentiation. In addition, we find that PD-1 suppresses Tfh cell differentiation and help for Ig class switching, even in the presence of wild-type Tfr cells. Our work points to critical roles for PD-L1 expressed on DCs in mediating PD-1 functions. |
Year of Publication | 2018
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Journal | J Immunol
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Volume | 200
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Issue | 8
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Pages | 2592-2602
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Date Published | 2018 04 15
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ISSN | 1550-6606
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DOI | 10.4049/jimmunol.1701231
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PubMed ID | 29531164
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PubMed Central ID | PMC6054131
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Grant list | P01 AI056299 / AI / NIAID NIH HHS / United States
R01 AI046414 / AI / NIAID NIH HHS / United States
R37 AI038310 / AI / NIAID NIH HHS / United States
T32 HL007627 / HL / NHLBI NIH HHS / United States
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