Anti-CD80 monoclonal antibody, clone 3B3

Objective Immune response initiation and regulation require activation of dendritic cells (DCs). However, the mechanism by which ferritin, a carrier for immunogen, induces DCs maturation remains unclear. Results Recombinant ferritin nanoparticle (RFNp), were prepared through the baculovirus expression vector system, formed spherical and hollow cage-liked proteins with a diameter of approximately 12.17 +/- 0.87 nm. They induced bone marrow-derived DC (BMDC) maturation via surface molecules up-regulation of (MHC II, CD80, CD86 and CD40), increased pro-inflammatory cytokines production (IL-6, IL-12, TNF-alpha, and IFN-gamma), and decreased antigen capturing capacity. They positively regulated I kappa B alpha and NF-kappa B (p65) phosphorylation, and facilitate NF-kappa B (p65) translocation into mature BMDCs nuclei. Following pre-treatment of RFNp-treated BMDCs with TLR4 and NF-kappa B (p65) inhibitors, respectively, surface molecule expression, pro-inflammatory cytokines production, and I kappa B alpha and NF-kappa B (p65) activities were suppressed. RFNp-treated BMDCs can also facilitate T-cell proliferation and differentiation into Th1 and Th2. Conclusion RFNps induced DCs maturation lends the potential application of RFNps as carrier platforms in DC-based vaccine.

Background. Although the outcome of kidney transplantation (KTx) has improved, various adverse effects of immunosuppressants and chronic rejection aggravate the long-term prognosis of patients. Therefore, the induction of immune tolerance may be an effective therapeutic strategy. Methods. A clinical trial aiming at immune tolerance induction was conducted in kidney transplant recipients from HLA mismatched living donors by infusing autologous donor-specific regulatory T cells (Treg). To obtain Treg, recipient's peripheral blood mononuclear cells were cocultured with irradiated donor cells in the presence of anti-CD80/CD86 monoclonal antibody for 2 weeks. For preconditioning, splenectomy + cyclophosphamide (CP) was employed in the first series (group A; n = 9). In group B, splenectomy was substituted by preadministration of rituximab (group B; n = 3). In the latest cases, rituximab + rabbit antithymocyte globulin was administered instead of cyclophosphamide (group C; n = 4). Twelve days after KTx, the cultured cells were intravenously infused, and immunosuppressants were gradually tapered thereafter. Results. Although mixed lymphocyte reaction was remarkably suppressed in a donor-specific fashion, 6 out of 9 patients from group A, 1 out of 3 from group B, and 1 out of 4 from group C developed acute rejection within 1 year after KTx. Complete cessation of immunosuppression was not achieved, and a small dose of immunosuppressants was continued. Conclusions. The adoptive transfer of autologous ex vivo-expanded Treg is 1 of the options to possibly induce alloimmune hyporesponsiveness. However, in the present study, further regimen optimization is still required and should be the focus of future investigations.