Heterogeneity of EAE mediated by multiple distinct T-effector subsets

Both TH1 and TH17 lymphocytes are implicated in inducing EAE. In mice lacking IFNγ, TH17 are assumed to be the subset responsible for inflammation induction. Here, we demonstrate that IFNγ KO mice have two additional effector subsets, one that up-regulates TH17-associated pro-inflammatory genes, but does not make IL-17 protein, and a second that utilizes IL-12-related elements of the TH1 pathway in an IFNγ-independent manner. In vivo, these two subsets induce demonstrably different disease. By using homogeneous T cell lines, we can dissect the population of autoimmune effector cells, and demonstrate the multiplicity of pro-inflammatory pathways important in disease processes.