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Induction of antigen-specific immunosuppression by CD95L cDNA-transfected 'killer' dendritic cells

Abstract

Dendritic cells (DCs) are special subsets of antigen-presenting cells characterized by their highly potent capacity to activate immunologically naive T cells. Here we report that DCs that are transfected with CD95 ligand (CD95L) cDNA, called 'killer' DCs, deliver death signals, instead of activation signals, to T cells after antigen-specific interaction. Injection of antigen-pulsed killer DCs into mice before sensitization induced antigen-specific immunosuppression. When administered after sensitization, killer DCs suppressed immune responses almost completely after subsequent challenge. Thus, killer DCs represent an entirely new immunomodulatory protocol, which may become directly applicable in preventing and even treating T cell-mediated inflammatory diseases.

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Figure 1: Expression of functional CD95L by XS106-CD95L DC clone.
Figure 2: In vitro functional properties of XS106-CD95L DC clone.
Figure 3: Effect of OVA-pulsed killer DCs on OVA-specific immune responses.
Figure 4: Effect of killer DCs on contact hypersensitivity responses.
Figure 5: Histological evaluation of the effect of killer DCs on contact hypersensitivity responses.
Figure 6: Therapeutic efficacy of killer DCs.

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Acknowledgements

We thank D. Thiele for suggestions in histological evaluation of liver toxicity and J. Forman and P.R. Bergstresser for comments. This study was supported by NIH grants (RO1-AR35068, RO1-AR43777, and RO1-AI43262) and by CE.R.I.E.S. Award (A.T.).

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Matsue, H., Matsue, K., Walters, M. et al. Induction of antigen-specific immunosuppression by CD95L cDNA-transfected 'killer' dendritic cells. Nat Med 5, 930–937 (1999). https://doi.org/10.1038/11375

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