Expression of programmed death (PD)-1 and PD-1 ligands (PD-L1, PD-L2) in peripheral blood mononuclear cells of patients with systemic lupus erythematosus

Background

Programmed death (PD)-1 is a newly described member of the immunoglobulin super-family that is expressed on activated T lymphocytes and B lymphocytes. Engagement of PD-1 with its specific ligands, PD-L1 (B7-H1) and PD-L2 (B7-DC), inhibits lymphocyte proliferation and cytokine expression, and may play a role in peripheral tolerance and negative regulation of T-cell and B-cell responses in vivo. We sought to investigate the expression profiles of PD-1 and PD-1 ligands in peripheral blood cells of patients with systemic lupus erythematosus (SLE).

Materials and methods

Blood was drawn from patients with SLE (n = 16), rheumatoid arthritis (n = 16), other inflammatory disease (n = 4), and healthy controls (n = 9). Peripheral blood mononuclear cells were separated on a ficoll-density gradient, and flow cytometry analysis was performed using monoclonal antibodies against CD3, CD19, CD14, CD25, CD69, PD-1, PD-L1, and PD-L2.

Results

See Table 1.

Table 1

Conclusions

In this preliminary report, SLE patients showed a trend for lower expression of PD-1 and higher expression of PD-L1 in unstimulated peripheral blood mononuclear cells compared with other disease controls. These results corroborate findings linking SLE with polymorphism of the PD-1 gene resulting in putative altered expression of the PD-L2 [1]. Lower expression of PD-1 in SLE lymphocytes could be related to ineffective suppression of autoreactive lymphocytes and thus to disease evolution. Currently, we investigate expression of PD-1 and its ligands on subpopulations of lymphocytes (CD45RO⁺, CD27⁺), as well as the kinetics of expression upon stimulation.