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  • Title: Tolerance of activated pathogenic CD4+ T cells by transcriptional targeting of dendritic cells.
    Author: de Andrade Pereira B, Ackermann M, Chaudhary S, Vogel R, Vogt B, Dresch C, Fraefel C.
    Journal: Gene Ther; 2015 May; 22(5):382-90. PubMed ID: 25739989.
    Abstract:
    We have recently shown that targeted expression of myelin oligodendrocyte glycoprotein (MOG) to dendritic cells with self-inactivating-lentivirus vectors induces antigen-specific tolerance in naive antigen-specific CD4+ T cells and protects mice from experimental autoimmune encephalomyelitis (EAE). In the present study, we demonstrate that this approach also induces tolerance of activated antigen-specific CD4+ T cells and completely protects mice from passive EAE induction. Tolerance induction did not correlate with the depletion of the preactivated antigen-specific CD4+ T cells. However, upon isolation and in vitro re-stimulation at day 6 after adoptive transfer the MOG-specific CD4+ T cells from the non-tolerized mice produced large amounts of inflammatory cytokines, whereas those from tolerized mice did not. This unresponsiveness correlated with the upregulation of regulatory molecules associated with anergy and regulatory T cells (Tregs). The in vivo depletion of Tregs resulted in EAE susceptibility of the tolerized animals, suggesting that these cells have indeed a role in tolerance induction/maintenance.
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