Dendritic cells (DCs) play a crucial role in the induction of antigen-specific immunity and tolerance. Considering in vivo application of DCs prior to human organ transplantation, a protocol to develop tolerogenic DCs that not only induce unresponsiveness in naive (CD45RA+) T cells, but also in alloreactive memory (CD45RO+) T cells is required. The present study shows that dexamethasone (Dex) alters the differentiation of human monocyte-derived DCs. DexDCs cocultured with allogeneic CD4+ T cells induced low proliferating and low IFNγ producing T cells. This is caused by lack of both costimulation via CD28 and hampered production of a soluble factor, as well as additional active suppression via B7-H1 and IL-10. T cells primed by DexDCs demonstrated hyporesponsiveness upon restimulation with mature DCs seemingly via the induction of anergy, since these cells showed no enhanced apoptosis and only a limited suppressive capacity. Interestingly, not only cocultures of allogeneic CD45RA+, but also of CD45RO+ T cells with DexDCs rendered T-cell populations hyporesponsive to restimulation with mature DCs. The finding that also alloreactive memory T cells can be regulated supports the rationale of cell-based therapies to obtain allograft-specific tolerance in transplant recipients.

, , , , ,,
American Journal of Transplantation
Department of Gastroenterology & Hepatology

Woltman, A., van der Kooij, S., de Fijter, J., & van Kooten, C. (2006). Maturation-resistant dendritic cells induce hyporesponsiveness in alloreactive CD45RA+ and CD45RO+ T-cell populations. American Journal of Transplantation, 6(11), 2580–2591. doi:10.1111/j.1600-6143.2006.01520.x