Low expressions of PD-L1 and CTLA-4 by induced CD4CD25 Foxp3 Tregs in patients with SLE and their correlation with the disease activity.

BACKGROUND

The induction of CD4CD25Foxp3 Treg from CD4CD25 T cells is deficient in the patients with systemic lupus erythematosus (SLE). Whether the induced CD4CD25Foxp3 Tregs possess defective function remains unclear. The purpose of the present research was to study the expression differences of functional membrane molecule between SLE patients and healthy controls by the induced CD4CD25Foxp3 Treg, in order to achieve a better understanding for the function deficiency of Treg in SLE.

METHODS

Peripheral blood mononuclear cells (PBMCs) isolated from healthy donors and SLE patients were used to separated CD4CD25 T cells. These CD4CD25 T cells were induced to differentiate into CD4CD25Foxp3 Tregs through incubating with CD3 and CD28 antibodies, TGF-β, IL-2 and rapamycin in vitro. Flow cytometry was applied to analyze the expressions of PD-1, PD-L1, CTLA-4, mTGF-β, LAP, CD39, mIL-10 and cIL-10, by the induced CD4CD25 T cells and the induced CD4CD25Foxp3 Tregs.

RESULTS

(1) The induced CD4CD25 T cells and the induced CD4CD25Foxp3 Tregs of both healthy controls and SLE patients both highly expressed PD-1. Nevertheless, the expressions of PD-L1 by the induced CD4CD25 T cells and the induced CD4CD25Foxp3 Tregs in SLE patients were significantly lower than those in healthy controls, which were negatively correlated with SLEDAI; (2) The expressions of CTLA-4 by the induced CD4CD25 T cells and the induced CD4CD25Foxp3 Tregs in SLE patients were also significantly reduced as compared with those in healthy controls, which were negatively correlated with SLEDAI; (3) As compared with healthy controls, the expressions of mTGF-β by the induced CD4CD25 T cells and the induced CD4CD25Foxp3 Tregs were also reduced in SLE patients, but there was no significant difference between active and inactive patients. While the expressions of LAP between SLE patients and healthy controls did not show significant difference; (4) The expressions of CD39 and mIL-10 displayed scarce significant differences between healthy controls and SLE patients, while the expressions of cIL-10 by the induced CD4CD25 T cells and the induced CD4CD25Foxp3 Tregs in SLE patients were significantly increased, which were not correlated with SLEDAI.

CONCLUSION

There were deficiencies in the expressions of PD-L1 and CTLA-4 in the induced CD4CD25Foxp3 Treg of SLE patients, which might be associated with the defective development and function of Treg involved in the pathological process of SLE.