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Exploring the transfer of experimental autoimmune encephalomyelitis using MOG TCR transgenic T cells
Author(s) -
Williams Jessica Lynn,
Kithcart Aaron,
Song Fei,
Gienapp Ingrid,
Shawler Todd,
Smith Kristen,
Whitacre Caroline
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1073.25
Subject(s) - myelin oligodendrocyte glycoprotein , experimental autoimmune encephalomyelitis , adoptive cell transfer , cd28 , immunology , multiple sclerosis , t cell receptor , t cell , biology , microbiology and biotechnology , immune system
Experimental autoimmune encephalomyelitis (EAE), a widely studied animal model for multiple sclerosis, is mediated by CD4+ T cells directed against myelin antigens such as myelin oligodendrocyte glycoprotein (MOG). A MOG T cell receptor transgenic (MOG Tg) mouse on a C57BL/6 background was recently reported. Difficulties have been encountered in transferring EAE using MOG Tg T cells. We explored a number of avenues for effecting transfer of disease such as varying culture time, density of cells in culture, antigen concentration and number of cells transferred with negative results in spite of robust proliferation and production of IFNγ. We hypothesized that encephalitogenic cells were being over‐stimulated and dying. Dilution of encephalitogenic cells with irradiated wildtype cells prior to transfer did not result in EAE transfer. Additionally, the cytokine cocktail was perhaps not adequately stimulating the encephalitogenic T cells. MOG Tg T cells were activated using IL‐2, IL‐7, IL‐12, IL‐18, and anti‐CD3/CD28 and pertussis toxin given to recipients. This protocol did not result in disease transfer. We are currently exploring additional cell activation parameters including generation of Th‐17 cells and suppressive mechanisms operative in the recipient. (Supported by NIH grant AI 064320, National MS Society grant RG3272 and NIH grant T32 AI055411)