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Published on: August 19, 2014
Tissue expression of PD-L1 mediates peripheral T cell tolerance
Mary E Keir1, Spencer C Liang, Indira Guleria
1Department of Pathology, Brigham and Women's Hospital and Children's Hospital Boston, MA 02115, USA.
The Journal of Experimental Medicine
|April 12, 2006
Summary
Programmed death 1 (PD-1) ligands PD-L1 and PD-L2 have overlapping roles in T cell regulation. PD-L1 uniquely protects the pancreas from autoimmune diabetes by inhibiting self-reactive T cells.
Area of Science:
- Immunology
- Autoimmunity
- Cellular Biology
Background:
- Programmed death 1 (PD-1) is an inhibitory receptor on lymphocytes regulating tolerance and autoimmunity.
- PD-1 has two ligands: PD-L1 (broad expression) and PD-L2 (restricted to antigen-presenting cells).
Purpose of the Study:
- To investigate the synergistic and unique roles of PD-L1 and PD-L2 in T cell activation and tolerance.
- To determine the specific contribution of PD-L1 and PD-L2 in autoimmune diabetes models.
Main Methods:
- Generated mice lacking both PD-L1 and PD-L2 (PD-L1/PD-L2(-/-)) for comparative studies.
- Utilized bone marrow chimeras and non-obese diabetic mouse models.
- Assessed T cell activation, cytokine production, and autoimmune diabetes onset.
Main Results:
- PD-L1 and PD-L2 exhibit overlapping functions in inhibiting T cell activation (IL-2, IFN-gamma production).
- PD-L1 plays a unique, critical role in controlling self-reactive T cells in the pancreas.
- PD-L1 expression on parenchymal cells, not hematopoietic cells, is crucial for preventing autoimmune diabetes.
Conclusions:
- PD-1-PD-L1 interactions on parenchymal cells mediate tissue tolerance and protect against autoimmune diabetes.
- PD-L1 expression in islets prevents immunopathology and tissue destruction mediated by self-reactive CD4+ T cells.
- Highlights a novel role for PD-L1 in maintaining pancreatic islet tolerance.
