Abnormality of circulating CD4(+)CD25(+) regulatory T cell in patients with Guillain-Barré syndrome.
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.
Chi
Li-Jun
LJ
Department of Neurology, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China.
Wang
Hua-Bing
HB
Zhang
Ying
Y
Wang
Wei-Zhi
WZ
D000293:Adolescent; D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D002648:Child; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D020275:Guillain-Barre Syndrome / Q000276:immunology* / Q000473:pathology* / Q000628:therapy; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D016756:Immunoglobulins, Intravenous