PD-L2 is expressed on activated human T cells and regulates their function.

Area of Science:

• Immunology
• Molecular Biology
• Cellular Signaling

Background:

• T-cell activation and proliferation are modulated by cosignaling molecules, which can provide positive or negative signals.
• Programmed death-1 (PD-1) is an inhibitory molecule on activated T cells and a key target in cancer immunotherapy.
• PD-1 ligands, PD-L1 and PD-L2, are typically found on antigen-presenting cells (APCs) mediating T-cell-APC interactions.

Purpose of the Study:

• To investigate the expression of PD-1 ligands, particularly PD-L2, on T cells themselves.
• To understand the functional role of PD-L2 expressed on T cells in regulating T-cell responses.

Main Methods:

• Analysis of PD-L2 expression on activated CD4 and CD8 T cell subsets.
• Assessment of PD-L2 engagement effects on T cell cytokine production and proliferation.

Main Results:

• PD-L2 expression was detected on activated CD4 and CD8 T cell subsets.
• Engagement of PD-L2 on T cells led to the downregulation of cytokine production.
• PD-L2 engagement also inhibited T cell proliferation.

Conclusions:

• PD-L2 is expressed by activated T cells, expanding its known cellular sources beyond APCs.
• T-cell-expressed PD-L2 plays a role in modulating T-cell function, including cytokine release and proliferation.
• These findings reveal a more intricate network of T-cell cosignaling, involving PD-L2 directly on T cells.