Expression of intracellular transforming growth factor-beta1 in CD4+CD25+ cells in patients with systemic lupus erythematosus
Ling-Ying Lu, Jiung-Jun Chu, Pei-Jung Lu, Ping-Kuang Sung, Chei-Mei Hsu, Jui-Cheng Tseng
Division of Allergy, Immunology, and Rheumatology and Department of Medical Research and Education, Kaohsiung Veterans General Hospital, Kaohsiung; and Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan
Received: September 1, 2006 Revised: February 7, 2007 Accepted: March 14, 2007
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).
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.
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.
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.
CD4-positive T-lymphocytes; Lupus erythematosus, systemic; T-lymphocytes, regulatory; Transforming growth factor-beta1
J Microbiol Immunol Infect. 2008;41:165-173.