THE SUSCEPTIBILITY OF MICE TO IMMUNE-MEDIATED NEUROLOGIC DISEASE CORRELATES WITH THE DEGREE TO WHICH THEIR LYMPHOCYTES RESIST THE EFFECTS OF BRAIN-DERIVED GANGLIOSIDES

SJL mice develop immune-mediated disorders of the central nervous syst em (CNS) when infected with certain neurotropic viruses or when immuni zed with myelin Ags. Other strains including BALB/c are more resistant to these diseases. During Sindbis virus-induced encephalitis, both mi ce are easily infected and elicit rapid mononuclear cell inflammation in the brain. However, only SJL mice develop immune-mediated paralysis ; BALB/c mice remain asymptomatic. To understand how the same stimulus produces such divergent immunologic effects on the host, the present study investigated lymphocytes that were isolated from the brains of S indbis virus-infected animals. Cells from the brains of SJL mice exhib ited more proliferation, produced more IL-2, maintained a higher viabi lity, and expressed less bar mRNA (a proapoptotic mediator) than did l ymphocytes from the brains of BALB/c mice. Since the central nervous s ystem is enriched in gangliosides that regulate T cell proliferation a nd IL-2 production in vitro, purified brain-derived gangliosides were tested on peripheral lymphocytes from both strains. These lipids had l ess of an effect on the mitogen-induced proliferation, IL-2 production , activation-induced cell death, and up-regulation of bas mRNA in lymp hocytes from SJL mice compared with those from BALB/c mice. Thus, gang liosides may inhibit various T cell effector functions and induce T ce ll apoptosis to a greater degree in the brains of BALB/c mice compared with the brains of SJL mice. This relative deficiency in local lympho cyte regulation may enhance the susceptibility of SJL mice to immune-m ediated neurologic disease.