Dendritic cells activate autologous T cells and induce IL-4 and IL-10 production in myasthenia gravis.
Dendritic cells (DC), as initiators and orchestrators of immune responses, control both naive and primed T cell responses. Depending on their maturation stage, DC promote immunity or tolerance. Here we investigated (1) the phenotype and cytokine secretion patterns of IL-10-modulated immature DC (IL-10-DC) and lipopolysaccharide (LPS)-driven mature DC (LPS-DC) in comparison with unmodulated immature DC (imDC) and (2) the effects of IL-10-DC, and of LPS-DC, vs. imDC on autologous T cell responses in patients with myasthenia gravis (MG) compared with healthy controls (HC). All three types of DC derived from MG significantly increased the levels of CD4+CD25+ T cells and of their subfraction expressing CD69, when compared to DC derived from HC. IL-10-DC induced production of IL-10 and IL-4 by T cells from MG patients, but only IL-10 production from HC. LPS-DC activated autologous T cells as reflected by augmented CD25, CD69 and CTLA-4 expression on CD4+ T cells, without differences between MG and HC. This was associated with increased production of both Th1 (IFN-gamma) and Th2 (IL-10 and IL-4) cytokines by T cells. These results indicate that DC-induced activation of autologous T cells is more pronounced in MG than in HC. In addition, DC-induced T cell responses in MG vs. HC are more Th2-prone.
Division of Neuroimmunology, Neurotec Department, Stockholm, Sweden.
Sanjaya Bandara
SB
Adikari
Ann Kari
AK
Lefvert
Ritva
R
Pirskanen
Rayomand
R
Press
Hans
H
Link
Yu-Min
YM
Huang
D000328:Adult; D000368:Aged; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D009157:Myasthenia Gravis / Q000276:immunology* / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*
D016753:Interleukin-10; D015847:Interleukin-4