FAILURE OF MATURE DENDRITIC CELLS OF THE HOST TO MIGRATE FROM THE BLOOD INTO CARDIAC OR SKIN ALLOGRAFTS

Abstract

Precisely where sensitization occurs after transplantation is uncertain, but it has been immunological dogma that sensitization to skin grafts occurs "centrally" in the draining lymph nodes. On the other hand, sensitization to fully-vascularized organs (kidney, heart, etc.) has been thought to occur "peripherally" within the graft itself. We have previously shown that mature dendritic cells migrate from the blood into the spleens of normal mice in a T cell-dependent manner, raising the possibility that circulating host dendritic leukocytes might be recruited from the blood into allografts where T cells had accumulated. This would provide a precedent for peripheral sensitization after transplantation. We examined whether 111indium-labeled mature DC host strain could migrate from the blood into cardiac or skin grafts. We were unable to detect migration into either allografts or isografts of these tissues, and found instead that the cells migrated to the spleen as in unmanipulated animals. This was despite the fact that accumulation of resting T cells was readily demonstrable in cardiac or skin allografts. In addition, we found that T cells sensitized against donor or third-party alloantigens had equal access to cardiac allografts, indicating that their migration into transplants is independent of their antigen specificity. The data of this study are discussed in the light of our other recent findings that donor DL migrate from fully-vascularized allografts into the recipients' spleens. Our current hypothesis is that allograft rejection is predominantly initiated centrally in host lymphoid tissues.