Abstract
We have shown that Hsp60sp-loaded immature dendritic cells (DC/sp) can protect mice from the induction of experimental allergic encephalomyelitis (EAE) by inducing Qa-1-restricted CD8+ T regulatory (Treg) cells. The binding half-life between Qa-1 and Hsp60sp is particularly short and leads to an unstable Qa-1/peptide complex that significantly decreases the efficacy of this vaccination. To prevent Qa-1/Hsp60sp complex dissociation, we utilized paraformaldehyde (PFA) fixation to stabilize the formation of the Qa-1/Hsp60sp complex and maximize the function of DC/sp as a vaccine to control autoimmune diseases. Compared with the non-fixed DC/sp, the fixed DC/sp (FDC/sp) showed an enhanced ability to activate Qa-1-restricted Hsp60sp-specific CD8+T cells in vitro and prevented EAE in vivo. Importantly, the FDC/sp maintained immune activity following cryopreservation for 1 week or after storage for 72 h at 4 °C. These results indicate that PFA fixation can sustain or increase the efficacy of DC/sp by improving the stability of the Qa-1/Hsp60sp complex on the surface of the DC/sp. In addition, PFA fixation creates a time window for DC/sp storage, transport and application. Our data suggest a potential clinical use of FDC/sp as a vaccine for the prevention and treatment of autoimmune disease.
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Acknowledgements
This work has been supported by the National Natural Science Foundation of China (NSF-30830093) and National Key Program (973) for Basic Research of China (2009CB522409) to HJ.
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Liu, F., Zheng, H., Qi, Y. et al. PFA-fixed Hsp60sp-loaded dendritic cells as a vaccine for the control of mouse experimental allergic encephalomyelitis. Cell Mol Immunol 11, 169–174 (2014). https://doi.org/10.1038/cmi.2013.58
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DOI: https://doi.org/10.1038/cmi.2013.58
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