Glial cells suppress postencephalitic CD8+ T lymphocytes through PD-L1

Area of Science:

• Neuroimmunology
• Immunology
• Cellular Biology

Background:

• Programmed death (PD)-1 receptor engagement by its ligand (PD-L1) suppresses T-lymphocytes.
• Microglia, brain's immune cells, regulate T-cell activation, impacting neuroinflammation.
• PD-L1 on microglia negatively regulates T-cell responses in models of central nervous system inflammation.

Purpose of the Study:

• Investigate the role of glial cell PD-L1 in controlling encephalitogenic CD8(+) T-lymphocytes during chronic neuroinflammation.
• Determine the impact of the PD-1: PD-L1 pathway on T-cell responses in a murine cytomegalovirus (MCMV) encephalitis model.

Main Methods:

• Utilized a murine model of chronic neuroinflammation induced by MCMV encephalitis.
• Performed in vitro co-culture experiments with primary murine microglia and CD8(+) T-cells.
• Analyzed ex vivo brain leukocytes from infected mice, including microglia and CD8(+) T-cells.

Main Results:

• Persisting CD8(+) T-cells in the brain expressed PD-1, while activated microglia expressed PD-L1.
• IFN-γ treatment upregulated PD-L1 on primary microglia.
• Blocking the PD-1: PD-L1 pathway increased T-cell IFN-γ and IL-2 production in co-cultures and ex vivo.

Conclusions:

• Microglia and astrocytes utilize the PD-1: PD-L1 pathway to control antiviral CD8(+) T-cell responses.
• Modulation of the PD-1: PD-L1 pathway holds therapeutic potential for managing detrimental neuroinflammation.