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


METHODS
Peripheral blood samples were obtained from 29 healthy subjects and 29 GBS patients.


METHODS
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 β-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.


CONCLUSIONS
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.
Department of Neurology, the Second Affiliated Hospital ofHarbin Medical University, Harbin, Helongjiang, PR China.
Song-lan
SL
Liang
Wei-zhi
WZ
Wang
Shuo
S
Huang
Xiao-kun
XK
Wang
Suang
S
Zhang
Yun
Y
Wu
D000328:Adult; D002454:Cell Differentiation / Q000276:immunology*; D005260:Female; D020275:Guillain-Barre Syndrome / Q000097:blood / Q000276:immunology* / Q000473:pathology; D000072597:Hepatitis A Virus Cellular Receptor 2; D006801:Humans; D007371:Interferon-gamma / Q000097:blood / Q000276:immunology; D020381:Interleukin-17 / Q000097:blood / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis / Q000276:immunology*; D008875:Middle Aged; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000096:biosynthesis / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D058504:Th17 Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D055815:Young Adult
C448908:HAVCR2 protein, human; D000072597:Hepatitis A Virus Cellular Receptor 2; C573415:IFNG protein, human; D020381:Interleukin-17; D008565:Membrane Proteins; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D012333:RNA, Messenger; C539900:RORC protein, human; D007371:Interferon-gamma