Cytokine profile of myelin basic protein—reactive T cells in multiple sclerosis and healthy individuals

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Abstract
Myelin basic protein (MBP)-reactive T cells have been implicated in the autoimmune pathogenesis of multiple sclerosis (MS). In this study, we examined the cytokine profile of 531 primary MBP-reactive T-cell lines and 72 independently established clones from 32 patients with MS and 18 healthy controls (NS) by using highly sensitive enzyme-linked immunosorbent assays. An increased number of primary T-cell lines producing interferon-γ (IFNγ) and/or interleukin-4 (IL-4) in response to MBP were found in patients with MS compared with controls. No distinct Th1 or Th2 subtypes could be demonstrated among the MBP-reactive clones. IL-4 was more frequently observed among MS-derived clones. Clones derived from MS patients produced increased levels of IL2, IL4, tumor necrosis factor-α (TNFα), IFNγ, and IL-10, but not IL-6. It is interesting that MBP-reactive T cells from MS patients expressing the disease-associated HLA-DRBI 15 allele produced increased quantities of TNFα, a cytokine suggested to play an important role in inflammation and demyelination. When challenged with either MBP or a bacterial superantigen, the clones expressed similar levels of the proinflammatory cytokine IFNγ. Our study suggests a functional difference in T-cell responses to MBP in patients with MS compared with healthy individuals, and provides further insights into the role of MBP-reactive T cells and their cytokine profile in the inflammatory processes of MS.