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Analysis of Autoreactive CD4 T Cells in Experimental Autoimmune Encephalomyelitis after Primary and Secondary Challenge Using MHC Class II Tetramers¹

Felix Bischof^2,3,*,, Matthias Hofmann^2,, Ton N. M. Schumacher, Florry A. Vyth-Dreese, Robert Weissert^*, Hansjörg Schild, Ada M. Kruisbeek^4, and Arthur Melms^4,*

^* Department of Neurology and Institute for Cell Biology, Department of Immunology, University of Tübingen, Tübingen, Germany; and Division of Immunology, Netherlands Cancer Institute, Amsterdam, The Netherlands

Experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, is primarily mediated by CD4 T cells specific for Ags in the CNS. Using MHC class II tetramers, we assessed expansion and phenotypic differentiation of polyclonal self-reactive CD4 T cells during EAE after primary and secondary challenge with the specific Ag. After EAE induction in SJL mice with proteolipid protein 139–151, CNS-specific T cells up-regulated activation markers and expanded in the draining lymph nodes and in the spleen. Less than 20% of total autoreactive T cells entered the CNS simultaneously with Th cells of other specificities. Almost all tetramer-positive cells in the CNS were activated and phenotypically distinct from the large peripheral pool. When EAE was induced in Ag-experienced mice, disease symptoms developed earlier and persisted longer; autoreactive T cells were more rapidly activated and invaded the CNS earlier. In striking contrast to specific CTLs that respond after secondary viral challenge, the absolute numbers of autoreactive CD4 T cells were not increased, indicating that the accelerated autoreactivity in Ag-experienced mice is not related to higher frequencies of autoreactive CD4 T cells.

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