MPA treatment of liver transplant patients may promote allograft tolerance in the long-term

Aims: Mycophenolate mofetil (MMF) is converted in the liver by ester hydrolysis to its active metabolite mycophenolic acid (MPA). Dendritic cell (DC) trafficking after organ transplantation constitutes an essential component in the process of allograft rejection. We investigated the effects of MPA on human blood myeloid DC (MDC) homeostasis with a particular emphasis on their trafficking properties. Methods: Isolated peripheral blood mononuclear cells (PBMC) from healthy donors were cultured with MPA for 48 hours without the addition of exogenous growth factors. Flow cytometry was used for phenotypic and functional analysis of MDC within the cultured PBMC population. Freshly isolated MDC were employed for assessment of endocytotic and allostimulatory properties. Results: Exposure to MPA lowered the expression of CC chemokine receptor (CCR)7 and increased the expression of CCR1 in MDC. In line with their CCR expression profile, MPA-treated MDC showed an enhanced migration towards inflammatory chemokines, whereas their migratory response towards lymph node chemokines decreased. MDC cultured with MPA exhibited an immature phenotype with higher endocytotic capacity, an impaired activation in response to toll-like receptor 3 ligation and loss of capacity to stimulate allogenic T cells in mixed lymphocyte reactions. Conclusion: MPA interferes with the initiation of acquired immunity, and thus may promote allograft tolerance.

allograft immune tolerance - liver transplantation - mycophenolate mofetil