Expression of intracellular transforming growth factor-beta1 in CD4+CD25+ cells in patients with systemic lupus erythematosus.
OBJECTIVE
The CD4+CD25+ regulatory T (Treg) cells exert immunoregulatory functions in various autoimmune diseases, in part through transforming growth factor-beta1 (TGF-beta1), and can be expanded by TGF-beta1 stimulation in normal subjects. This study aimed to examine intrinsic TGF-beta1 expression and the response to TGF-beta1 stimulation of this CD4+CD25+ subset in patients with systemic lupus erythematosus (SLE).


METHODS
Flow cytometry with multicolor staining of CD4+, CD25+, and TGF-beta1 was used to quantify the percentage of CD4+CD25+ T cells in fresh peripheral blood and TGF-beta1-stimulated peripheral blood mononuclear cell (PBMC) cultures, and their corresponding intracellular TGF-beta1 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-beta1 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-beta1 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-beta1 expression of CD4+CD25+ cells of SLE were normalized to the levels of the control group. In TGF-beta1-stimulated PBMC cultures, CD4+CD25+ cells and their intracellular TGF-beta1 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-beta1 expression by TGF-beta1 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-beta1 expression or in response to TGF-beta1 stimulation in patients with SLE. This study suggests that TGF-beta1, by inducing CD4+CD25+ cells, has potential clinical application in treating SLE.
Lu
Ling-Ying
LY
Division of Allergy, Immunology, and Rheumatology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan. lylu@vghks.gov.tw
Chu
Jiung-Jun
JJ
Lu
Pei-Jung
PJ
Sung
Ping-Kuang
PK
Hsu
Chei-Mei
CM
Tseng
Jui-Cheng
JC
D000328:Adult; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000503:physiopathology*; D008297:Male; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*; D013624:Taiwan; D053773:Transforming Growth Factor beta1 / Q000097:blood / Q000235:genetics / Q000276:immunology*
D053773:Transforming Growth Factor beta1