T helper cell type 1 (Th1), Th2 and Th17 responses to myelin basic protein and disease activity in multiple sclerosis

Autoreactive T cells are thought to play an essential role in the pathogenesis of multiple sclerosis (MS). We examined the stimulatory effect of human myelin basic protein (MBP) on mononuclear cell (MNC) cultures from 22 patients with MS and 22 sex-matched and age-matched healthy individuals, and related the patient responses to disease activity, as indicated by magnetic resonance imaging. The MBP induced a dose-dependent release of interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) by patient-derived MNCs. The patients' cells produced higher amounts of IFN-gamma and TNF-alpha, and lower amounts of IL-10, than cells from healthy controls (P<0.03 to P<0.04). Five patients with MS and no controls, displayed MBP-induced CD4+ T-cell proliferation. These high-responders exhibited enhanced production of IL-17, IFN-gamma, IL-5 and IL-4 upon challenge with MBP, as compared with the remaining patients and the healthy controls (P<0.002 to P<0.01). A strong correlation was found between the MBP-induced CD4+ T-cell proliferation and production of IL-17, IFN-gamma, IL-5 and IL-4 (P<0.0001 to P<0.01) within the patient group, and the production of IL-17 and IL-5 correlated with the number of active plaques on magnetic resonance images (P=0.04 and P=0.007). These data suggest that autoantigen-driven CD4+ T-cell proliferation and release of IL-17 and IL-5 may be associated with disease activity. Larger studies are needed to confirm this.