Quantitative and qualitative deficiencies of regulatory T cells in patients with systemic lupus erythematosus (SLE)

Abstract

The objective of the study was that the regulatory T cells (Treg) that specialize in the suppression of immune responses might be critically involved in the pathogenesis of autoimmune disease. As for systemic lupus erythematosus (SLE), however, published data concerning Treg phenotype and function are partly conflicting. We therefore performed quantitative and qualitative analyses of naturally occurring CD4(+)CD25(+) Treg from SLE patients as compared with healthy controls (HC) in order to further elucidate the role of Treg in this systemic autoimmune disease. The phenotype of peripheral blood CD4(+)CD25(+) Treg was determined by flow cytometry (FACS) in SLE patients and HC. Treg were isolated from SLE patients and HC and their functional capacity was analyzed in suppression assays. Phenotypic and functional data were correlated with clinical data. Decreased proportions of CD4(+) Treg with high-level expression of CD25 (CD4(+)CD25(hi)) were observed in active and inactive SLE patients (0.96 +/- 0.08 and 1.17 +/- 0.08%, respectively) as compared with HC (2 +/- 0.1%). In contrast to HC, Treg from SLE patients displayed an activated phenotype as determined by the expression of CD69, CD71 and HLA-DR. The suppressive capacity of isolated Treg from SLE patients, however, was significantly reduced as compared with HC. Proportions of CD4(+)CD25(hi) T cells and the suppressive capacity of Treg were inversely correlated with the clinical disease activity in SLE patients. Our data describe quantitative and qualitative defects of Treg in SLE patients. These deficiencies might contribute to the breakdown of self-tolerance and the development of the autoimmune response in SLE patients.

Peripheral blood regulatory T cells in patients with diffuse systemic sclerosis (SSc) before and after autologous hematopoietic SCT: a pilot study

“…2,7 The various Treg cells have key roles in maintaining self-tolerance and modulating the allergic and autoimmune responses, while controlling autoreactive T cells. [8][9][10][11] Several studies have reported a deficiency in the number of Treg and/or function in autoimmune disease patients, 12,13 namely in systemic lupus erythematous, 14 rheumatoid arthritis, 15 multiple sclerosis, 16 autoimmune polyglandular syndrome II, 17 myasthenia gravis 18 and type I diabetes. 19 However, results concerning the number of circulating Treg cells and their suppressive function have been contradictory.…”

Inactivation of Notch signaling reverses the Th17/Treg imbalance in cells from patients with immune thrombocytopenia

“…13 Recent studies found that missing or dysfunction of Treg cells can lead to a variety of autoimmune diseases such as SLE and RA. 14,15 The balance of Th17/Treg controls immune response and has been reported to be a key factor in regulating Th cell function relating to the Th1/Th2 shift in autoimmune diseases and graft vs host disease. 16 Emerging evidence suggests that Th17/Treg imbalances contributes to the development of autoimmune diseases, such as SLE 17 and primary nephrotic syndrome.…”

T Cell Targeted Therapies in Lupus: Do They Make Sense?

“…In addition to upregulated effector T cell responses, SLE patients have reduced numbers and impaired function of CD4+ regulatory T cells (Treg) [11]. An imbalance between Th17 cells and Treg, with higher ratio of Th17 to Treg cells compared to healthy controls has also been reported in SLE [12•].…”