FIGURE 4.

Stable Th17 cells induce ON. (A) Intracellular cytokine production by CD4⁺ T cells derived from MOG-immunized IL-12KO mice, after 96 hours of culture with MOG_35-55 and recombinant IL-23. (B) Intracellular cytokine production by CD4⁺ T cells derived from MOG-immunized IL-12KO donors after infiltrating the spinal cords and optic nerves of IL-12KO hosts. (C) Clinical courses of IL-12KO mice injected with myelin-specific CD4+ Th17 cells derived from IL-12KO donors versus WT mice injected with WT effector Th17 cells. The data shown is pooled from 3 experiments with n=10 WT and n=17 IL12KO host mice per group. (D) The percentage of CD4⁺ T cells and CD11b⁺ myeloid cells among CD45⁺ leukocytes infiltrating the optic nerve and spinal cord of IL-12KO hosts shortly after the onset of clinical EAE. (E) Contiguous sections of an optic nerve obtained from an IL-12KO host at clinical EAE onset and stained with CD45 (red, top left panel) or SMI-32 (green). (F) A representative section stained with toludine blue (bars= 50μm in D, 25μm in E). Areas with normal appearing axons are outlined, asteriscs indicate swollen axons and arrowheads point to empty myelin sheaths. (G–I) CAPs were measured in acutely isolated optic nerves from the IL-12KO recipients of stable Th17 cells at clinical EAE onset. (G) Representative wave-forms of optic nerve CAPs from a naïve IL-12KO mouse and an IL-12KO adoptive transfer recipient with acute ON. The data were averaged over seven to nine nerves per group. Data are presented as mean ±S.E.M. (*p<0.05, **p<0.01; Mann-Whitney)