Myelin oligodendrocyte glycoprotein (MOG)‐specific T cells mediate an autoimmune inflammatory response in the central nervous system (CNS) that differs radically from conventional models of T cell‐mediated experimental allergic encephalomyelitis (EAE). Using synthetic peptides an encephalitogenic T cell epitope of MOG for the Lewis rat was identified within the extracellular IgG V‐like domain of the protein, amino acids 44‐53 (FSRVVHLYRN).The adoptive transfer of CD4⁺ T cells specific for this epitope induce an intense, dose‐dependent inflammatory response in the CNS of naive syngeneic recipients. However, unlike the inflammatory response induced by myelin basic protein (MBP)‐specific T cell lines, inflammation mediated by the MOG peptide‐specific T cells failed to induce a gross neurological deficit.

This unexpected observation was not due to a reduction in the overall inflammatory response in the CNS, but was specifically associated with a decrease in the extent of parenchymal (as opposed to perivascular) inflammation, a selective decrease in the number of ED1⁺ macrophages infiltrating the CNS, and a total lack of peripheral nerve inflammation. The decreased recruitment of macrophages into the CNS could not be ascribed to deficiences in the synthesis of interferon‐γ, tumor necrosis factor‐a, interleukin (IL)‐6 or IL‐2 by the T cell line. Moreover, this sub‐clinical inflammatory response induced severe blood‐brain barrier dysfunction as demonstrated by the induction of severe clinical disease following intravenous injection of a demyelinating MOG‐specific monoclonal antibody. The neurological deficit in EAE thus exhibits an unexpected dependence on the identity of the target autoantigen, which determines the extent and nature of the local inflammatory response and ultimately the extent of the neurological deficit.