Heterogeneity of EAE mediated by multiple distinct T-effector subsets

Both T_H1 and T_H17 lymphocytes are implicated in inducing EAE. In mice lacking IFNγ, T_H17 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 T_H17-associated pro-inflammatory genes, but does not make IL-17 protein, and a second that utilizes IL-12-related elements of the T_H1 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.