The effect of PD-1/PD-L1 signaling axis on the interaction between CD19+B cells and CD4+T cells in peripheral blood of patients with systemic lupus erythematosus

Abstract

Background: The defect of B cell self-tolerance and the continuous antigen presentation by T cells (TCs) mediated by autoreactive B cells (BCs) play a key role in the occurrence and development of systemic lupus erythematosus (SLE). PD-1/PD-L1 signaling axis negatively regulates the immune response of TCs after activation and maintains immune tolerance. However, the effect of PD-1/PD-L1 signaling axis on the interaction between CD19⁺B/CD4⁺TCs in the peripheral blood of patients with SLE has not been studied in detail.

Methods: PD-1/PD-L1 and Ki-67 levels in peripheral blood (PB) of 50 SLE patients and 41 healthy controls (HCs) were detected through flow cytometry, and then the expression of PD-1^+/-cells and PD-L1^+/-cells Ki-67 was further analyzed. CD19⁺B/CD4⁺TCs were separated for cell culture and the supernatant was collected to determine proliferation and differentiation of TCs. IL-10 and IFN-γ secretion in the supernatant was also determined using ELISA.

Results: The PD-1, PD-L1, and Ki-67 levels on CD19⁺B/CD4⁺TCs in patients with SLE were higher than HCs. In CD19⁺B/CD4⁺TCs of SLE patients, the proliferative activity of PD-L1⁺ cells was higher than that of PD-L1^- cells, and the proliferative activity of PD-1⁺ cells was higher than that of PD-1^- cells. In the system co-culturing CD19⁺B/CD4⁺TCs from HCs/SLE patients, activated BCs promoted TCs proliferation and PD-L1 expression among TCs. Addition of anti-PD-L1 to co-culture system restored the proliferation of TCs, and inhibited IL-10/IFN-γ level. The addition of anti-PD-L1 to co-culture system also restored Tfh and downregulated Treg in HCs.

Conclusions: Axis of PD-1/PD-L1 on CD19⁺B/CD4⁺TCs in PB of SLE patients is abnormal, and cell proliferation is abnormal. In CD19⁺B/CD4⁺TCs of SLE patients, the proliferative activity of PD-L1⁺ and PD-1⁺ cells compared with PD-L1^- and PD-1^- cells in SLE patients, respectively. CD19⁺B/CD4⁺TCs in SLE patients can interact through PD-1/PD-L1.

Keywords: CD19+B cells; CD4+T cells; Ki-67; PD-1/PD-L1 signal axis; SLE.