[Hypothetical view on the environmental factors, Th1/Th2 balance, and disease phenotype of MS/EAE]

The optico-spinal form of multiple sclerosis (MS) seems to be no more predominant in Japan. Instead, the proportion of the conventional MS is as large as that seen in Caucasian population, probably due to the change in life style or environmental factors. Here I discuss on the environmental factors that might have influenced on the change in the disease phenotypes. It is reasonable to speculate that Japanese people are now exposed to antigens that were not prevalent 30 years ago. The "new" antigens may cross-stimulate autoimmune T cells that are responsible for forming demyelinating lesions in the brain but not in the spinal cord. On the other hand, the young Japanese might have missed encountering certain bacterial antigens in the childhood that is necessary to establish the properly balanced T cell repertoire. The modern Japanese is reported to have the immune repertoire that is relatively Th2-biased. The Th2 shift may account for the more frequent development of the conventional MS in the young Japanese. To support this idea, I point out that the mice that tend to mount a Th2 response would develop brain lesions after induction of EAE, whereas the Th1 mice would develop spinal cord lesions.