Th17 helper cell and T-cell immunoglobulin and mucin domain 3 involvement in Guillain-Barré syndrome.

ABSTRACT

OBJECTIVE AND DESIGN: We investigated the involvement of Th17 cells and T-cell immunoglobulin and mucin domain 3 (TIM-3) in Guillain-Barré syndrome (GBS) in comparison to healthy subjects. MATERIALS AND SUBJECTS: Peripheral blood samples were obtained from 29 healthy subjects and 29 GBS patients. TREATMENT Peripheral blood mononuclear cells (PBMCs) and CD4(+) T cells were stimulated with anti-CD3 and anti-CD28 mAbs, in the absence or presence of anti-TIM-3 mAb. METHODS: mRNA levels of TIM-3 and the transcription factor retinoic acid-related orphan receptor γt (RORγt) were determined by RT-PCR and were expressed relative to ß-actin mRNA (housekeeping gene). Serum IFN-γ and IL-17 levels were determined by ELISA. RESULTS: Compared to controls, relative TIM-3 mRNA levels were lower in both stimulated and unstimulated PBMCs from GBS patients. Unstimulated GBS CD4(+) T cells and GBS CD4+ T cells stimulated with anti-CD3 and CD28 mAbs had higher relative RORγt mRNA expression compared to controls. GBS CD4(+) T cells secreted significantly more IFN-γ and IL-17 in the presence of anti-TIM-3 mAb. GBS patients had (1) higher numbers of Th17, but not Th1 or Th2 cells in peripheral blood and (2) higher serum concentrations of IFN-γ and IL-17 compared to controls. CONCLUSION: TIM-3 may inhibit Th17 cell activation, thereby modulating their cytokine secretion patterns. Th17 cell differentiation, IL-17 levels, and TIM-3 regulation may be involved in the pathogenesis of GBS.