title: PFA-fixed Hsp60sp-loaded dendritic cells as a vaccine for the control of mouse experimental allergic encephalomyelitis.
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.
authors.forename: Feng
authors.initials: F
authors.lastname: Liu
authors.forename: Hui
authors.initials: H
authors.lastname: Zheng
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Qi
authors.forename: Xue
authors.initials: X
authors.lastname: Wang
authors.forename: Jianjun
authors.initials: J
authors.lastname: Yang
authors.forename: Miaomiao
authors.initials: M
authors.lastname: Han
authors.forename: Han
authors.initials: H
authors.lastname: Zhang
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D018834:Chaperonin 60 / Q000276:immunology / Q000378:metabolism*; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000637:transplantation; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000517:prevention & control; D005557:Formaldehyde / Q000494:pharmacology; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000378:metabolism*; D011108:Polymers / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D014612:Vaccines
chemical_list: D018834:Chaperonin 60; D015395:Histocompatibility Antigens Class I; D010446:Peptide Fragments; D011108:Polymers; C032907:Q surface antigens; D014612:Vaccines; D005557:Formaldehyde; C003043:paraform