Cross-Tolerance of Recipient-Derived Transforming Growth Factor-Beta Dendritic Cells

Administration of donor-derived immature dendritic cells (DC) treated with transforming growth factor-beta (TGF-β) to prevent allograft rejection is not applicable for clinical use. We therefore attempted to explore the use of recipient-derived DC pulsed with donor antigens via the indirect pathway (cross-priming). DC were propagated from C3H (H2^k) bone marrow (BM) using granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin-4 (IL-4). TGF-β (0.2 ng/mL) was added at the initiation of culture. The resultant TGF-β DC were pulsed with B10 (H2^b) splenocyte lysate. Expression of major histocompatibility complex (MHC) class I and II was not affected, while CD40, CD80, and CD86 costimulatory molecules on DC were significantly inhibited by treatment with TGF-β. C3H DC pulsed with B10 antigens stimulated a proliferative response in C3H T cells which was inhibited when DC were treated with TGF-β, and the cytotoxic T-lymphocyte (CTL) activity was also inhibited. This observation correlated with reduced interferon-gamma (IFN-γ) and increased IL-10 production. A single injection of TGF-β DC prolonged allograft survival (median survival time [MST] 18 days vs 10 days in no-DC treatment control; P < .05). These data indicated that an approach utilizing recipient DC as a "vaccine" strategy is possible.