In vivo roles of donor and host dendritic cells in allogeneic immune response: cluster formation with host proliferating T cells.

Possible roles of dendritic cells (DCs) in allogeneic immune responses in host lymphoid tissues were characterized in situ by using rat DC transfer and cardiac transplantation models. When allogeneic DCs were intravenously injected, these cells selectively migrated to the T-cell area of hepatic lymph nodes, with peak accumulation at 18 h after injection. Donor DCs and proliferating host T cells formed clusters (rosettes) in which the T-cell proliferative response started. The donor DCs were CD80(+) CD86(+) and, ultrastructurally, were in intimate contact with lymphoblasts within the rosettes. As a novel finding, some of the migrated donor DCs were quickly phagocytosed by putative host interdigitating DCS: By 48 h, the remaining donor DCs had disintegrated within the rosettes. Host interdigitating DCs also formed rosettes throughout the T-cell area, and their kinetics correlated well with that of the T-cell proliferation. In the cardiac allograft model, a few donor DCs selectively migrated to the host spleen and hepatic nodes. Rosette formation by donor and host DCs, phagocytosis of donor DCs, and the T-cell proliferative response occurred in much the same fashion as they did in the first experiment. We conclude that the donor rosettes at the early stage represent the sites of direct allosensitization and those at the late stage represent donor-DC killing. Host rosettes are the sites of T-cell proliferation. In this structure, phagocytosed donor-DC-derived antigens are presumably indirectly presented.