PD-1/PD-Ls pathways between CD4(+) T cells and pleural mesothelial cells in human tuberculous pleurisy

Area of Science:

• Immunology
• Cell Biology
• Infectious Diseases

Background:

• Programmed death 1 (PD-1) and its ligands (PD-L1, PD-L2) are implicated in tuberculosis immunity.
• The role of PD-1/PD-L pathways in pleural mesothelial cells (PMCs) and CD4(+) T cells within tuberculous pleural effusion (TPE) remains uncharacterized.

Purpose of the Study:

• To investigate the expression and regulation of the PD-1/PD-L pathway in PMCs and CD4(+) T cells in TPE.
• To determine the impact of this pathway on CD4(+) T cell functions, including proliferation, apoptosis, adhesion, and migration.

Main Methods:

• Quantification of PD-1 on CD4(+) T cells and PD-L1/PD-L2 on PMCs in TPE samples.
• Comparison of PD-1/PD-L expression in TPE versus blood and transudative effusions.
• Assessment of interferon-γ's effect on PD-1/PD-L expression.
• Evaluation of PD-1/PD-L pathway blockade on CD4(+) T cell proliferation and adhesion.

Main Results:

• Soluble PD-1 levels were elevated in TPE compared to serum.
• PD-1 expression on CD4(+) T cells and PD-L1/PD-L2 expression on PMCs were significantly higher in TPE.
• Interferon-γ upregulated PD-1 on CD4(+) T cells and PD-Ls on PMCs.
• Blocking the PD-1/PD-L pathway reversed the inhibitory effects on CD4(+) T cell proliferation and adhesion.

Conclusions:

• The PD-1/PD-L pathway is upregulated in TPE and actively suppresses CD4(+) T cell proliferation and adhesion.
• Mycobacterium tuberculosis likely utilizes the PD-1/PD-L pathway on PMCs to evade host immune responses in the pleural space.