Abnormality of circulating CD4(+)CD25(+) regulatory T cell in patients with Guillain-Barré syndrome

Abstract

CD4(+)CD25(+) T regulatory cells (Tregs), a subset of CD4(+) T cells expressing high levels of CD25 and the transcription factor Foxp3, are critical in maintaining immunologic homeostasis and preventing autoimmunity by suppressing self-reactive T cells. Guillain-Barré syndrome (GBS) is thought to be a self-limiting, autoimmune disease of the peripheral nervous system. We hypothesized that altered frequency and/or function of Tregs play a role in the breakdown of immunologic self-tolerance in GBS patients. To characterize Tregs in GBS patients, we used flow cytometry to evaluate peripheral numbers of Tregs, real-time polymerase chain reaction to assay mRNA expression of FOXP3, and coculture to analyze functional suppressive properties of Tregs. The results showed that acute-stage patients with AMAN and AIDP exhibited significantly reduced numbers of peripheral Tregs as compared with healthy donors, but marked improvement was observed in stable-stage patients with GBS after treatment with intravenous immunoglobulin (IVIG), concomitantly with improvement of neuropathic symptoms. On the other hand, GBS-derived Tregs and Tregs from healthy individuals exhibited equal FOXP3-expression of mRNA and their ability of suppressing the proliferation and cytokine secretion of CD4 (+) effector T cells was unimpaired in GBS patients. These results suggest that short-term reduced circulating Tregs may be associated with the pathogenesis of two subtypes of GBS. Reversible number and intact function of Tregs presumably contribute to monophasic self-limiting course in GBS.