T cell reactivities to myelin protein-derived peptides in neuromyelitis optica patients with anti-aquaporin-4 antibody

We previously reported the establishment of major myelin protein-derived T cell lines from 11 patients with multiple sclerosis. In the present study, we determined anti-aquaporin-4 (AQP4) antibody status in these patients and classified them into five patients with anti-AQP4 antibody who met the criteria for neuromyelitis optica (NMO) or NMO spectrum disorders, and six patients without anti-AQP4 antibody who fulfilled the revised McDonald criteria for multiple sclerosis. T cell lines reactive to myelin oligodendrocyte glycoprotein, proteolipid protein and myelin basic protein were detected in 5/5, 3/5 and 3/5 of the anti-AQP4 antibody-positive patients, respectively, and in 5/6, 4/6 and 4/6 of the anti-AQP4 antibody-negative ones, respectively. T cell lines from most of these patients showed inter- or intra-molecular epitope spreading, irrespective of anti-AQP4 antibody status. These findings suggest that T cells are stimulated in vivo against major myelin proteins in anti-AQP4 antibody-positive patients with NMO/NMO spectrum disorders.