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.
| Disease group | ||||||||
|---|---|---|---|---|---|---|---|---|
| Healthy controls | Systemic lupus erythematosus | Rheumatoid arthritis | Inflammatory disease | |||||
| Mean | SEM | Mean | SEM | Mean | SEM | Mean | SEM | |
| PD-1+ (%) | ||||||||
| in CD3+ | 0.6 | 0.2 | 0.4 | 0.1 | 1.6 | 0.6 | 0.5 | 0.1 |
| in CD19+ | 1.7 | 0.9 | 1.4 | 0.3 | 0.9 | 0.4 | 1.1 | 0.4 |
| in CD25+ | 3.0 | 1.0 | 2.4 | 0.7 | 3.3 | 1.6 | 8.5 | 3.4 |
| PD-L1+ (%) | ||||||||
| in CD3+ | 2.8 | 1.2 | 4.1 | 0.9 | 2.3 | 0.5 | 2.0 | 0.6 |
| in CD19+ | 3.9 | 1.3 | 5.1 | 0.9 | 3.7 | 1.0 | 11.3 | 8.0 |
| in CD14+ | 5.1 | 2.0 | 14.0 | 5.4 | 2.9 | 0.9 | 5.7 | 3.2 |
| PD-L2+ (%) | ||||||||
| in CD3+ | 0.6 | 0.2 | 0.5 | 0.1 | 0.5 | 0.2 | 0.4 | 0.0 |
| in CD14+ | 2.0 | 0.5 | 1.4 | 0.3 | 1.1 | 0.5 | 1.2 | 0.1 |
SEM, standard error of the mean. No statistically significant differences were observed.
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.
References
- Prokunina L, Castillejo-Lopez C, Oberg F, Gunnarsson I, Berg L, Magnusson V. A regulatory polymorphism in PDCD1 is associated with susceptibility to systemic lupus erythematosus in humans. Nat Genet. 2002;32:666–669. doi: 10.1038/ng1020. [DOI] [PubMed] [Google Scholar]