CD8+ T cell help is required for efficient induction of EAE in Lewis rats

• We investigated the role of CD8+ T cells in the EAE of the Lewis rat.
• Complete depletion or genetic ablation of CD8+ T cells protects Lewis rats from EAE.
• Reduced infiltration of leukocytes into the CNS in the absence of CD8+ T cells
• CD8-deficiency interferes with the generation of encephalitogenic CD4+ T cells.

The role of CD8+ T cells in multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) is still unclear. We describe here significantly reduced disease activity of EAE both in Lewis rats depleted of CD8+ T cells by monoclonal antibodies and CD8 knockout rats, which was accompanied by reduced leukocyte infiltration into the spinal cord. We detected myelin basic protein (MBP)-specific CD4+ T cells in peripheral lymphoid organs of CD8-depleted animals which, however, failed to differentiate into interferon-γ-producing effector cells. Our results indicate that CD8+ T cells interact with myelin-specific CD4+ T cells early in EAE enabling them to differentiate into pathogenic effector cells.