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 h ost lymphoid tissues were characterized in situ by using rat DC transfer an d cardiac transplantation models, When allogeneic DCs were intravenously in jected, these cells selectively migrated to the T-cell area of hepatic lymp h nodes, with peak accumulation at 18 h after injection, Donor DCs and prol iferating host T cells formed clusters (rosettes) in which the T-cell proli ferative response started. The donor DCs were CD80(+) CD86(+) and, ultrastr ucturally, were in intimate contact with lymphoblasts within the rosettes, As a novel finding, some of the migrated donor DCs were quickly phagocytose d by putative host interdigitating DCs, By 48 h, the remaining donor DCs ha d disintegrated within the rosettes, Host interdigitating DCs also formed r osettes throughout the T-cell area, and their kinetics correlated well with that of the T-cell proliferation. In the cardiac allograft model, a few do nor 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 r epresent the sites of direct allosensitization and those at the Late stage represent donor-DC killing, Host rosettes are the sites of T-cell prolifera tion. In this structure, phagocytosed donor-DC-derived antigens are presuma bly indirectly presented.