T cell skewing toward a TH17 or TH1 phenotype directs inflammation to the brain or spinal cord. (a) Representative CD4 (red) and F4/80 (green) staining of cerebellum and lumbar spinal cord sections of F1 recipients of epitope-specific T cells (the atypical:classic EAE ratios were rMOG, 3:0; MOG35–55, 0:6; MOG79–90, 2:7; MOG97–114, 11:0). Scale bar, 200 µm. (b) The distribution of inflammation between brain and spinal cord, as quantified by image analysis software, was significantly different for all specificities (P < 0.0001). Error bars indicate s.d. (c) Percentage of F1 recipients showing atypical or classic EAE after transfer of T cells cultured with either peptide alone, peptide and IL-12, or peptide and IL-23 (n = 5–11 recipients per group). Some IL-23–skewed T cell recipients with atypical EAE also showed tail paralysis (3/10, 2/5 and 4/6 for MOG97–114-, MOG79–90- and MOG35–55-specific T cells, respectively). Atypical EAE incidence was significantly higher for non-skewed MOG97–114- compared with MOG79–90- (P = 0.0001) and MOG35–55-specific T cells (P = 0.0003). The difference in disease phenotype induced by IL-23– and IL-12–skewed cells was significant (P = 7.7 × 10−19). (d) Immunohistochemical staining for CD4+ and F4/80+ cells in representative brain and spinal cord sections from IL-12– or IL-23–skewed MOG97–114-specific T cell recipients. Scale bar, 200 µm. (e) Flow cytometric analyses of recipients in c revealed significantly more CD4+, F4/80+, Gr-1+ and CD11c+ cells in the brains of atypical compared with classic EAE mice (P ≤ 0.04). Error bars represent s.e.m.