Decoy NF-κB fortified immature dendritic cells maintain laryngeal allograft integrity and provide enhancement of regulatory T cells

Objectives/Hypothesis: The increased risk of malignancy associated with post-transplant immunosuppression limits the potential of laryngeal transplantation as a reconstructive option. This risk may be mitigated by utilizing decoy nuclear factor kappa B (NF-κB) immature dendritic cells (iDC) to provide donor-specific tolerance. The purpose of this study was to explore whether tolerogenic properties of iDC can be applied to composite tissue transplantation. Study Design: Animal study. Methods: Five iDC-injected mice were euthanized at 15, 30, and 60 days post-laryngeal transplant. Control groups included five transplanted mice without immunosuppression, one iDC-injected mouse euthanized prior to transplantation, one mouse without injection or transplantation, and one mouse administered mature DC to serve as an accelerated rejection control. Larynges were graded for rejection severity according to a grading scale. Draining lymph nodes and spleens were evaluated by flow cytometry to determine immunogenic activity of iDC and T cells locally and peripherally. Results: Each time group demonstrated moderate allograft rejection (rejection severity scores: 4.38, 5.10, 5.29). NF-κB iDC-treated mice had significantly less rejection at all time points compared to nonimmunosuppressed mice. Flow cytometry showed inhibition of cytotoxic T cell infiltration and expansion of regulatory T cells at the allograft site. Conclusions: iDC immunosuppression maintains laryngeal allograft integrity up to 60 days posttransplantation. Regulatory T cells are enhanced at the allograft site, which serves to suppress immune cell activation and induce self-antigen tolerance. iDC injection may lessen post-transplant comorbidities by decreasing the systemic immune response and favorably affecting concurrent immunosuppressive dose sequencing for laryngeal allograft preservation.