Cytokine mRNA Profile of Myelin Basic Protein Reactive T-cell Clones in Patients with Multiple Sclerosis

Abstract

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 TNFα and IL-10 mRNA, these differences do not reach statistical significance. Interestingly, significantly increased TNFα and IFNγ 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 TNFα and IFNγ 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.