Expression of intracellular transforming growth factor-betal in CD4 ⁺CD25⁺ cells in patients with systemic lupus erythematosus

Background and Purpose: The CD4⁺CD25⁺ regulatory T (Treg) cells exert immunoregulatory functions in various autoimmune diseases, in part through transforming growth factor-beta1 (TGF-β1), and can be expanded by TGF-β1 stimulation in normal subjects. This study aimed to examine intrinsic TGF-β1 expression and the response to TGF-β1 stimulation of this CD4⁺CD25⁺ subset in patients with systemic lupus erythematosus (SLE). Methods: Flow cytometry with multicolor staining of CD4⁺, CD25⁺, and TGF-β1 was used to quantify the percentage of CD4⁺CD25⁺ T cells in fresh peripheral blood and TGF-β1-stimulated peripheral blood mononuclear cell (PBMC) cultures, and their corresponding intracellular TGF-β1 expression. Results: In fresh peripheral blood, we found that decreased percentages of CD4⁺CD25⁺/CD4⁺ in SLE patients were associated with disease activity and renal involvement. Intracellular TGF-β1 expression of CD4⁺CD25⁺ cells was significantly elevated in SLE compared with matched controls (p<0.001). In addition, there was significant negative correlation between TGF-β1 expression and percentage of CD4⁺CD25⁺ cells present (r = -0.432, p=0.004). Nevertheless, in ex vivo unstimulated PBMC cultures, the percentage and intracellular TGF-β1 expression of CD4⁺CD25⁺ cells of SLE were normalized to the levels of the control group. In TGF-β1- stimulated PBMC cultures, CD4⁺CD25⁺ cells and their intracellular TGF-β1 expression were significantly increased (p<0.001), both in SLE and controls. Moreover, the increments in the percentage of CD4 ⁺CD25⁺ cells and intracellular TGF-β1 expression by TGF-β1 stimulation were comparable in SLE and controls, and were not significantly influenced by disease activity or renal involvement in SLE. Conclusions: CD4⁺CD25⁺ cells were deficient in peripheral blood but not impaired either in intrinsic TGF-β1 expression or in response to TGF-β1 stimulation in patients with SLE. This study suggests that TGF-β1, by inducing CD4⁺CD25⁺ cells, has potential clinical application in treating SLE.