BACKGROUND: Regulatory dendritic cells (Reg-DCs), which induce regulatory T cells and interleukin (IL)-10 in vitro, are capable of inducing immunogenic tolerance in vivo. In this study, we assessed whether Reg-DCs modulate the course of autoimmune processes in a murine model of autoimmune gastritis (AIG). METHODS: AIG mice were produced by neonatal thymectomy of 3-day old BALB/c mice followed by administration of polyinosinic:polycytidylic acid (poly I:C). Reg-DCs were produced by culturing bone marrow DCs with IL-10, lipopolysaccharide, and parietal cell (PC) antigen for 2 days. In the course of development of AIG, BALB/c mice were administered either Reg-DCs, mature DCs, or phosphate-buffered saline, intraperitoneally, four times. The levels of gastritis and autoantibody to PC antigen were assessed serially in these mice. RESULTS: The stages of gastritis and the titers of autoantibody to PC antigen were significantly lower in Reg-DC-treated mice than in mature DC-treated mice (P<0.05). Spleen cells from Reg-DC-treated mice produced increased levels of IL-10 and decreased levels of IL-12p70 and interferon-gamma (P<0.05). Also, frequencies of IL-10-producing CD4(+)CD25(+) T cells in the spleen and Foxp3(+)CD4(+)CD25(+) T cells in the peripheral blood were significantly higher in Reg-DC-treated mice than in mature DC-treated mice (P<0.05). CONCLUSIONS: Taken together, these results suggest that increased induction of CD4(+)CD25(+) regulatory T cells by Reg-DCs might contribute to downregulation of inflammatory processes and autoantibody production during AIG development in mice.
BACKGROUND: Regulatory dendritic cells (Reg-DCs), which induce regulatory T cells and interleukin (IL)-10 in vitro, are capable of inducing immunogenic tolerance in vivo. In this study, we assessed whether Reg-DCs modulate the course of autoimmune processes in a murine model of autoimmune gastritis (AIG). METHODS: AIG mice were produced by neonatal thymectomy of 3-day old BALB/c mice followed by administration of polyinosinic:polycytidylic acid (poly I:C). Reg-DCs were produced by culturing bone marrow DCs with IL-10, lipopolysaccharide, and parietal cell (PC) antigen for 2 days. In the course of development of AIG, BALB/c mice were administered either Reg-DCs, mature DCs, or phosphate-buffered saline, intraperitoneally, four times. The levels of gastritis and autoantibody to PC antigen were assessed serially in these mice. RESULTS: The stages of gastritis and the titers of autoantibody to PC antigen were significantly lower in Reg-DC-treated mice than in mature DC-treated mice (P<0.05). Spleen cells from Reg-DC-treated mice produced increased levels of IL-10 and decreased levels of IL-12p70 and interferon-gamma (P<0.05). Also, frequencies of IL-10-producing CD4(+)CD25(+) T cells in the spleen and Foxp3(+)CD4(+)CD25(+) T cells in the peripheral blood were significantly higher in Reg-DC-treated mice than in mature DC-treated mice (P<0.05). CONCLUSIONS: Taken together, these results suggest that increased induction of CD4(+)CD25(+) regulatory T cells by Reg-DCs might contribute to downregulation of inflammatory processes and autoantibody production during AIG development in mice.
Authors: A Nishio; T Katakai; C Oshima; S Kasakura; M Sakai; S Yonehara; T Suda; S Nagata; T Masuda Journal: Gastroenterology Date: 1996-10 Impact factor: 22.682