Myelin antigen-specific CD8(+) T cells are encephalitogenic and produce severe disease in C57BL/6 mice

Encephalitogenic T cells that mediate experimental autoimmune encephalomyel itis (EAE) are commonly assumed to be exclusively CD4(+), but formal proof is still lacking. In this study, we report that synthetic peptides 35-55 fr om myelin oligodendrocyte glycoprotein (pMOG(35-55)) consistently activate a high proportion of CD8(+) alpha beta TCR+ T cells that are encephalitogen ic in C57BL/6 (B6) mice. The encephalitogenic potential of CD8(+) MOG-speci fic T cells was established by adoptive transfer of CD8-enriched MOG-specif ic T cells. These cells induced a much more severe and permanent disease th an disease actively induced by immunization with pMOG(35-55). CNS lesions i n pMOG(35-55) CD8(+) T cell-induced EAE were progressive and more destructi ve. The CD8(+) T cells were strongly pathogenic in syngeneic B6 and RAG-1(- /-) mice, but not in isogeneic beta (2)-microglobulin-deficient mice. MOG-s pecific CD8(+) T cells could be repeatedly reisolated for up to 287 days fr om recipient B6 or RAG-1(-/-) mice in which disease was induced adoptively with < 1 X 10(6) T cells sensitized to pMOG(35-55). It is postulated that M OG induces a relapsing and/or progressive pattern of EAE by eliciting a T c ell response dominated by CD8(+) autoreactive T cells. Such cells appear to have an enhanced tissue-damaging effect and persist in the animal for long periods.