Nishimura T, Onda M, Takao S. CD4+ CD25+ regulatory T cells suppressed the indirect xenogeneic immune response mediated by porcine epithelial cell pulsed dendritic cells. Xenotransplantation 2010; 17: 313–323. © 2010 John Wiley & Sons A/S.
Abstract: Background: CD4+ CD25+ regulatory T cells have been reported to suppress T cell-mediated xenogeneic immune responses. Although the direct T cell response to xenogeneic cells is important, the indirect xenogeneic immune response mediated by dendritic cells (DCs) is also likely involved in rejection. We have generated an in vitro indirect immune reaction model and evaluated the effect of CD4+ CD25+ regulatory T cells on this system.
Methods: Human DCs were generated from peripheral blood and cultured with X-ray-irradiated porcine kidney epithelial cells. Porcine cell-pulsed DCs were mixed with autologous CD4+ T cells, CD4+ CD25− T cells and/or CD4+ CD25+ T cells. After 7 days of culture, T cell proliferation was measured.
Results: The co-culture of human DCs and X-ray-irradiated porcine epithelial cells resulted in observable DC phagocytic activity within 2 days. These porcine cell–pulsed DCs stimulated CD4+ T cell proliferation much more potently than unpulsed DCs or porcine cells. This proliferation was blocked by CTLA4-Ig or an anti-HLA-DR antibody. CD4+ CD25+ regulatory T cells also suppressed CD4+ CD25− T cell proliferation in response to porcine cell-pulsed DCs.
Conclusions: An in vitro model of the indirect xenogeneic immune response was established. Porcine cell-pulsed DCs stimulated CD4+ T cells, and CD4+ CD25+ regulatory T cells suppressed this response.