In vitro modeling of early donor-recipient immune interactions for liver graft tolerance: Evaluation of soluble CD83 modulation

Lifelong immunosuppression remains a major challenge in pediatric liver transplantation, underscoring the need for strategies that promote immune tolerance. This study aimed to model early donor–recipient immune interactions in vitro and assess the immunomodulatory potential of soluble CD83 (sCD83). Peripheral blood mononuclear cells from 18 liver transplant recipients were stimulated with anti-CD3/CD28 and donor liver homogenates, followed by co-culture of activated T cells with naïve B cells and T follicular helper cells in a transwell system, with or without sCD83 treatment. After 9 days, gene expression of CIITA and FOXP3 was analyzed by qPCR, and cytokine levels (IL-6, IL-10, IL-21) were measured via ELISA. While sCD83 did not suppress T cell activation, co-cultures with activated T cells resulted in significant downregulation of CIITA in B cells, suggesting early plasma cell differentiation, with no change in FOXP3 expression. Notably, cytokine analysis revealed reduced IL-6 and elevated IL-10 levels, indicating a shift toward a regulatory immune phenotype. This patient-derived co-culture model effectively simulates early alloimmune responses and highlights a context-dependent immunomodulatory role of sCD83, warranting further investigation using diverse cellular and organoid systems.