Myelin-Specific Cd8 T Cells in the Pathogenesis of Experimental Allergic Encephalitis and Multiple Sclerosis

Experimental autoimmune encephalomyelitis (EAE) serves as the prototypic model for T cell–mediated autoim-munity. EAE has striking similarities with the human disease acute disseminated encephalomyelitis, a complication seen with vaccination and after certain viral infections. EAE has been used as a model to help understand the pathogenesis of multiple sclerosis (MS) and to help identify potential therapeutic candidates for this disease (Table I), Until now, research has focused nearly exclusively on the role of CD4 ϩ T cells in EAE (1–3). In this issue and in a recent publication in the Journal of Immunology (4, 5), a pathogenic role of CD8 T cells in EAE has now been described. Lesions in inflammatory infiltrates in the brain and spinal cord of MS patients (6, 7), and in brain lesions in EAE (8), include both CD4 and CD8 T cells. Therefore, it is important to seriously consider both of these T cell subsets in the evolution of this mysterious disease which afflicts nearly a million individuals worldwide. Over 4,500 papers have been published on the EAE model since it was first described (9, 10). The Journal of Experimental Medicine has published many of the landmark papers on EAE, dating back Ͼ 60 yr to the publication of River's classic paper on the induction of encephalomyelitis in primates with extracts from rabbit brain (11). Kabat's description of the use of Freund's adjuvant in the induction of EAE appeared in The Journal of Experimental Medicine 54 yr ago (12). The use of Complete Freund's Adjuvant to induce EAE reduced the number of injections required in River's model from 85 over 1 yr to a single injection of brain extract (12)! The use of Freund's Adjuvant to initiate EAE probably induced biases in the types of cells that expanded after such immunization. T cells that could be expanded after injection of Complete Freund's Adjuvant were mostly Th1, probably due to the CpG motifs in the DNA from the killed mycobacteria tuberculosis. Thus, via history and peer selection The Journal of Experimental Medicine has traditionally been the forum for new developments in this model. Until now almost all of the work done in the EAE model has focused on CD4 T cells and the resulting cascade of cytokines and chemokines involved in pathogene-sis. Recently, again in this journal, LaFaille and Tonegawa showed that CD4 ϩ , myelin-specific T cells induced EAE predominantly, but not always, via production …