Deficient CD4+ CD25high T regulatory cell function in patients with active systemic lupus erythematosus

X Valencia, C Yarboro, G Illei… - The Journal of …, 2007 - journals.aai.org
X Valencia, C Yarboro, G Illei, PE Lipsky
The Journal of Immunology, 2007journals.aai.org
Abstract CD4+ CD25+ T regulatory cells (Tregs) play an essential role in maintaining
immunologic homeostasis and preventing autoimmunity. Systemic lupus erythematosus
(SLE) is a systemic autoimmune disease characterized by a loss of tolerance to nuclear
components. We hypothesized that altered function of CD4+ CD25 high Tregs might play a
role in the breakdown of immunologic self-tolerance in patients with SLE. In this study, we
report a significant decrease in the suppressive function of CD4+ CD25 high Tregs from …
Abstract
CD4+ CD25+ T regulatory cells (Tregs) play an essential role in maintaining immunologic homeostasis and preventing autoimmunity. Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by a loss of tolerance to nuclear components. We hypothesized that altered function of CD4+ CD25 high Tregs might play a role in the breakdown of immunologic self-tolerance in patients with SLE. In this study, we report a significant decrease in the suppressive function of CD4+ CD25 high Tregs from peripheral blood of patients with active SLE as compared with normal donors and patients with inactive SLE. Notably, CD4+ CD25 high Tregs isolated from patients with active SLE expressed reduced levels of FoxP3 mRNA and protein and poorly suppressed the proliferation and cytokine secretion of CD4+ effector T cells in vitro. In contrast, the expression of FoxP3 mRNA and protein and in vitro suppression of the proliferation of CD4+ effector T cells by Tregs isolated from inactive SLE patients, was comparable to that of normal individuals. In vitro activation of CD4+ CD25 high Tregs from patients with active SLE increased FoxP3 mRNA and protein expression and restored their suppressive function. These data are the first to demonstrate a reversible defect in CD4+ CD25 high Treg function in patients with active SLE, and suggest that strategies to enhance the function of these cells might benefit patients with this autoimmune disease.
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