Redistribution of rat renal allograft-responding leukocytes during rejection: 1. Model

We describe a model that enables us to trace the traffic of allograft-responding inflammatory leukocytes to and from the graft without handling of these cells in vitro. At different times after transplantation, the kidney transplant pedicle—including the artery, vein, and draining lymphatics—is clamped. The allograft-responding leukocytes are labeled by a [³H]thymidine pulse either in situ or in the systemic lymphoid organs of the recipient. Fifteen minutes later the pulse is chased with a 1000-fold excess of cold thymidine, and the clamp is opened. The animals are sacrificed 18 hr later, when a balance between the synthesis of new labeled leukocytes from the originally labeled ones and dilution of intracellular label has been achieved. This model was used to analyze the allograft-responding inflammatory cell traffic to and from a renal transplant performed across the major histocompatibility complex in the rat. A sizable traffic was observed to both directions: After systemic injection of label only 0.008 × 10⁶ labeled cells × hr^?1 were found to emigrate into a kidney allograft (control). Already on the third day after transplantation—when the in situ inflammatory response is still at its beginning—more than 0.3 × 10⁶ labeled cells × hr^?1 migrated from the host to the allograft and 1.6 × 10⁶ labeled cells × hr^?1 left the allograft to the recipient spleen. The first figure is several-fold higher than any previous estimate. The findings emphasize the systemic nature of the antiallograft inflammatory response.