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

D Sun, JN Whitaker, Z Huang, D Liu… - The Journal of …, 2001 - journals.aai.org
D Sun, JN Whitaker, Z Huang, D Liu, C Coleclough, H Wekerle, CS Raine
The Journal of Immunology, 2001journals.aai.org
Encephalitogenic T cells that mediate experimental autoimmune encephalomyelitis (EAE)
are commonly assumed to be exclusively CD4+, but formal proof is still lacking. In this study,
we report that synthetic peptides 35–55 from myelin oligodendrocyte glycoprotein (pMOG 35–
55) consistently activate a high proportion of CD8+ αβTCR+ T cells that are
encephalitogenic in C57BL/6 (B6) mice. The encephalitogenic potential of CD8+ MOG-
specific T cells was established by adoptive transfer of CD8-enriched MOG-specific T cells …
Abstract
Encephalitogenic T cells that mediate experimental autoimmune encephalomyelitis (EAE) are commonly assumed to be exclusively CD4+, but formal proof is still lacking. In this study, we report that synthetic peptides 35–55 from myelin oligodendrocyte glycoprotein (pMOG 35–55) consistently activate a high proportion of CD8+ αβTCR+ T cells that are encephalitogenic in C57BL/6 (B6) mice. The encephalitogenic potential of CD8+ MOG-specific T cells was established by adoptive transfer of CD8-enriched MOG-specific T cells. These cells induced a much more severe and permanent disease than disease actively induced by immunization with pMOG 35–55. CNS lesions in pMOG 35–55 CD8+ T cell-induced EAE were progressive and more destructive. The CD8+ T cells were strongly pathogenic in syngeneic B6 and RAG-1−/− mice, but not in isogeneic β 2-microglobulin-deficient mice. MOG-specific CD8+ T cells could be repeatedly reisolated for up to 287 days from recipient B6 or RAG-1−/− mice in which disease was induced adoptively with< 1× 10 6 T cells sensitized to pMOG 35–55. It is postulated that MOG induces a relapsing and/or progressive pattern of EAE by eliciting a T cell 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.
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