Reactivity pattern and cytokine profile of T cells primed by myelin peptides in multiple sclerosis and healthy individuals.

Abstract

Autoreactive T cells specific for candidate myelin antigens, including myelin basic protein (MBP) and proteolipid protein (PLP), are thought to play an important role in the pathogenesis of multiple sclerosis (MS). Myelin-reactive T cells primed in vivo by myelin breakdown products or microbial cross-reactive antigens during the disease processes may exhibit a reactivity pattern and cytokine profile different from those in the normal T cell repertoire. In this study, we examined the precursor frequency, the reactivity pattern and cytokine profile of myelin-reactive T cells that were primed in vitro with overlapping peptides of MBP and PLP in patients with MS and healthy individuals. The results revealed that T cells specific for peptides of MBP and PLP occurred at a relatively higher precursor frequency in patients with MS than that in healthy individuals. We identified a number of dominant T cell epitopes within MBP and PLP, some of which were not previously detected using whole myelin antigens as the primary stimuli. Some residues represented common immunodominant regions that were detected in both MS patients and healthy controls while others were associated only with MS. MBP-reactive T cell lines generally exhibited a Th0-like cytokine profile. There was significantly increased Th1 cytokine production (i. e. TNF and IFN-gamma) among MS-derived T cell lines. PLP-reactive T cell lines had a distinct cytokine profile, producing predominantly TNF-alpha and little or not IFN-gamma and IL-4. The findings have important implications in the understanding of the role of myelin-reactive T cells in MS.