Gender differences in autoimmune demyelination in the mouse: implications for multiple sclerosis

Abstract

Gender-related differences in experimental allergic encephalomyelitis (EAE) were examined in the SJL mouse with the purpose of characterizing an animal model ideal for the study of gender-related differences in multiple sclerosis (MS). For the model to allow for study of the induction and the effector phase of disease, the adoptive EAE model was characterized. First, the SJL strain was shown to be nonresponsive with regard to the development of antisyngeneic HY-specific responses in females, thereby permitting intergender adoptive transfers of T lymphocytes during EAE induction. Then, when myelin basic protein (MBP)-specific T cells derived from females were adoptively transferred into female and male recipients, female recipients demonstrated a more rapid onset of disease (p = 0.01), greater maximal acute-phase clinical scores (p < 0.0001) and greater mean clinical scores (p < 0.0001) compared with male recipients. When MBP-specific T cells derived from males were adoptively transferred, female recipients again tended to be more severely affected. Histopathologic analysis revealed quantitative differences between genders that paralleled clinical expression. These results document a clear gender-related difference in adoptive EAE in the SJL, with clinical and histopathologic disease greater in females compared with males. This model will be a useful tool for addressing autoimmune mechanisms underlying gender-related differences in MS.