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Volume 41, Number 2, April 2008

Expression of intracellular transforming growth factor-beta1 in CD4+CD25+ cells in patients with systemic lupus erythematosus

Ling-Ying Lu1, Jiung-Jun Chu1, Pei-Jung Lu2,3, Ping-Kuang Sung1, Chei-Mei Hsu1, Jui-Cheng Tseng1
1Division of Allergy, Immunology, and Rheumatology and 2Department of Medical Research and Education, Kaohsiung Veterans General Hospital, Kaohsiung; and 3Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan

Received: September 1, 2006      Revised: February 7, 2007       Accepted: March 14, 2007

Corresponding author: Dr. Ling-Ying Lu, M.D., Division of Allergy, Immunology, and Rheumatology, Kaohsiung Veterans General Hospital, 386 Ta-chung 1st Rd, Kaohsiung 813, Taiwan. E-mail: This e-mail address is being protected from spam bots, you need JavaScript enabled to view it

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.

Key words: CD4-positive T-lymphocytes; Lupus erythematosus, systemic; T-lymphocytes, regulatory; Transforming growth factor-beta1


J Microbiol Immunol Infect. 2008;41:165-173.
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