Intrinsic ability of GM+IL-4 but not Flt3L-induced rat dendritic cells to promote allogeneic T cell hyporesponsiveness

The influence of GM + IL-4 and Flt3 ligand (FL) on phenotype and function of BM-derived DC from Lewis rats was investigated. GM + IL-4-induced DC, despite expression of CD80/ CD86, were less stimulatory than FL-induced DC that expressed tow CD80/CD86 and were efficient stimulators of allogeneic T cells. GM + IL-4 DC were CD11b(+) OX62(lo), whereas FL DC were CD11b(lo) OX62(+). Following activation, GM + IL-4 DC produced IL-10 and IL-6, but no IL-12p70, and were resistant to further maturation. FL DC produced IL-12p70, IFN-alpha/beta, IL-10 and IL-6 and underwent maturation. Repeated stimulation of T cells with GM + IL-4 DC inhibited proliferation, cytokine production and induced early T cell apoptosis. FL DC-activated T cells produced large amounts of IFN-gamma/IL-10 and exhibited late T cell apoptosis/ necrosis. In vivo, GM + IL-4 DC induced alloAg-specific hyporesponsiveness following T cell restimulation. These results demonstrate that GM + IL-4 DC display intrinsic regulatory properties, inducing passive-cell-death in T cells with potential for inactivation/ regulation of alloreactive T cells in transplantation. (C) 2006 Elsevier Inc. All. rights reserved.