Cytokine mRNA profile of myelin basic protein reactive T-cell clones in patients with multiple sclerosis.
Autoimmune mechanisms involving T-cell responses to (a) myelin autoantigen(s), such as myelin basic protein (MBP), are thought to contribute to the pathogenesis of multiple sclerosis (MS). Cytokines may play a central role in the regulation of the pathogenic autoimmune responses in MS and the mediation of tissue damage in the disease. To study the cytokine expression of myelin reactive T-cells in MS, we determined the cytokine mRNA levels in a panel of blood derived MBP-specific T-cell clones derived from MS patients (33 clones) and normal controls (21 clones), using a novel quantitative RT-PCR method. Our results demonstrate that MBP-specific T-cells, both from MS patients and control subjects, predominantly display a Th1- or Th0-like cytokine pattern. Although MS clones express higher levels of TNFalpha and IL-10 mRNA, these differences do not reach statistical significance. Interestingly, significantly increased TNFalpha and IFNgamma mRNA levels were observed among clones derived from HLA-DR2 positive versus HLA-DR2 negative MS patients. This HLA halpotype is known to be associated with MS. The high levels of TNFalpha and IFNgamma mRNA observed in MBP-reactive T-cell clones from MS patients indicate an important role of these cytokines in the disease process. Our data lend further support to the pathogenic role of MBP-reactive T-cells in MS.
Department of Immunology, Dr. L. Willems-Instituut, Universitaire Campus, Diepenbeek, Belgium.
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Vandevyver
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Motmans
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Stinissen
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Zhang
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Raus
D000328:Adult; D001324:Autoantigens / Q000276:immunology; D002999:Clone Cells / Q000276:immunology; D016207:Cytokines / Q000235:genetics*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015870:Gene Expression; D019672:Genes, T-Cell Receptor / Q000235:genetics; D015802:HLA-DR2 Antigen / Q000032:analysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000276:immunology*; D004676:Myelin Basic Protein / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D001324:Autoantigens; D016207:Cytokines; D015802:HLA-DR2 Antigen; D004676:Myelin Basic Protein; D012333:RNA, Messenger