Multiple sclerosis is associated with high levels of circulating dendritic cells secreting pro-inflammatory cytokines.
Recent evidence emphasises a pivotal role for dendritic cells (DC) in the control of immunity by priming and tolerising T cells. DC capture and process antigens, express co-stimulatory molecules, migrate to lymphoid organs and secrete cytokines to initiate immune responses. In multiple sclerosis (MS), autoreactive T cells are proposed to play a pathogenic role by secreting pro-inflammatory cytokines, but studies on DC are lacking. To evaluate the involvement of DC in patients with MS, a modified procedure was used to prepare DC from blood of patients with MS and healthy subjects. DC were found to be potent stimulators of T cells in allogeneic and, to a lesser extent, in autologous mixed leukocyte reaction (MLR). Enzyme-linked immunospot (ELISPOT) assays were adopted to determine levels of IFN-gamma, TNF-alpha, IL-6 and IL-10 secreting DC vs. mononuclear cells (MNC). Proportionally more DC than MNC secreted IFN-gamma and IL-10 in both MS and healthy subjects. Patients with MS had higher levels of IFN-gamma, TNF-alpha and IL-6 secreting DC than healthy subjects. The differences for IFN-gamma and TNF-alpha secreting cells were confined to the subgroup of untreated MS patients and not observed in the subgroup examined during ongoing treatment with IFN-beta. Circulating DC secreting pro-inflammatory cytokines may represent another focus for the study of both immuno-pathogenesis and therapeutic interventions in MS.
Huang
Y M
YM
Karolinska Institute, Division of Neurology, Unit of Neuroimmunology, Huddinge University Hospital, Stockholm, Sweden. yu-min.huang@neurotec.ki.se
Xiao
B G
BG
Ozenci
V
V
Kouwenhoven
M
M
Teleshova
N
N
Fredrikson
S
S
Link
H
H
D000328:Adult; D000368:Aged; D000818:Animals; D001327:Autoimmune Diseases / Q000097:blood* / Q000276:immunology; D016207:Cytokines / Q000097:blood / Q000378:metabolism*; D003713:Dendritic Cells / Q000378:metabolism*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000097:blood / Q000378:metabolism; D016753:Interleukin-10 / Q000097:blood / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood / Q000378:metabolism; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D051379:Mice; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood* / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000378:metabolism
D016207:Cytokines; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma