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- W4313356304 abstract "Abstract Previous studies showed that GM-CSF-deficient (Csf2-deficient, Csf2−/−) mice exhibited profound resistance to experimental autoimmune encephalomyelitis (EAE). The present study focused on the myelin oligodendrocyte glycoprotein (MOG) 35–55-specific model of murine EAE in Csf2-deficient and wildtype C57BL/6 mice. The study addressed whether disease resistance of Csf2-deficient mice reflected a role for GM-CSF in controlling the functional balance between effector and regulatory T cells. The main finding was that treatment with the anti-CD25 mAb PC61 rendered Csf2-deficient mice fully susceptible to severe EAE, similar to that of C57BL/6 mice. When both donors and recipients were treated with PC61 in a passive model of EAE, adoptive transfer of myelin-specific Csf2−/− T cells into Csf2−/− recipients resulted in chronic severe EAE. Csf2-deficient T cell repertoire was characterized by elevated CD3+ T cell frequencies that reflected accumulations of naïve CD44null-low CD4+ and CD8+ T cells but normal frequencies of CD4+ CD25+ FOXP3+ T cells. Overall, this finding suggested that Csf2−/− mice had secondary deficiencies in T cell sensitization to environmental antigens. In accordance, MOG35-55/ Complete Freund’s Adjuvant -sensitized Csf2−/− mice exhibited deficient peripheral sensitization to MOG, whereas pretreatment of sensitized Csf2−/− mice with PC61 enabled the robust induction of MOG-specific T cell responses in the draining lymphatics. In conclusion, the EAE resistance of Csf2−/− mice, at least in part, reflects deficient induction of effector T cell function that cannot surmount normal Treg barriers. EAE effector responses in Csf2-deficient mice however are unleashed upon depletion of regulatory CD25+ T cells." @default.
- W4313356304 created "2023-01-06" @default.
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- W4313356304 date "2017-05-01" @default.
- W4313356304 modified "2023-09-23" @default.
- W4313356304 title "GM-CSF controls the balance between effector and regulatory T cell lineage in experimental autoimmune encephalomyelitis (EAE)" @default.
- W4313356304 doi "https://doi.org/10.4049/jimmunol.198.supp.132.1" @default.
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