Tolerance of activated pathogenic CD4+T cells by transcriptional targeting of dendritic cells

作者：Pereira B de Andrade; Ackermann M; Chaudhary S; Vogel R; Vogt B; Dresch C; Fraefel C^*

来源：Gene Therapy, 2015, 22(5): 382-390.

DOI：10.1038/gt.2015.6

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/maintenace.

• 出版日期2015-5