IL-12/IL-12R system in multiple sclerosis.
IL-12/IL-12 receptor (IL-12R) system orchestrates the Th1 pathway of the immune system by maintaining one of the major bridges between innate and adaptive immune responses. Here, we studied both sides of this system in patients with multiple sclerosis (MS) and in controls. MS patients displayed elevated IL-12Rbeta1 and IL-12Rbeta2 expression on PHA-activated T cells compared to healthy subjects. Higher percentages of IL-12Rbeta1 and IL-12Rbeta2 positive T cells in cerebrospinal fluid (CSF) compared to blood were observed both in MS and other neurological diseases (OND). In contrast, numbers of IL-12 secreting blood mononuclear cells (MNC) were similar in MS and controls. The functional importance of high IL-12Rbeta2 in MS was underlined by the finding that IL-12 stimulated IFN-gamma production and proliferation of PHA-activated T cells correlated with levels of IL-12Rbeta2 expression. Our data indicates a dysregulation of the IL-12/IL-12R system in MS. It is suggested that even in the absence of increased IL-12 levels, the net effect of IL-12 might be augmented in MS by elevated expression of its receptor.
Ozenci
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V
Neuroimmunology Unit, Division of Neurology, Karolinska Institutet, Huddinge University Hospital, Stockholm, Sweden. volkan.ozenci@neurotec.ki.se
Pashenkov
M
M
Kouwenhoven
M
M
Rinaldi
L
L
Söderström
M
M
Link
H
H
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000134:cerebrospinal fluid / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid / Q000276:immunology*; D010835:Phytohemagglutinins / Q000494:pharmacology; D018123:Receptors, Interleukin / Q000276:immunology*; D053707:Receptors, Interleukin-12; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
D010835:Phytohemagglutinins; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D018664:Interleukin-12; D007371:Interferon-gamma