In situ effector mechanisms in rat kidney allograft rejection. III. Kinetics of the inflammatory response and generation of donor-directed killer cells.
We have isolated and identified the infiltrating inflammatory cells from rejecting rat kidney allografts. The first host cells to appear in the graft, already a few hours after the transplantation, are monocytes and lymphocytes. Both T and B lymphocytes contribute to the infiltrate: at early stages of rejection most of the infiltrating lymphocytes have the high electrophoretic mobility of (resting) T cells, whereas later during the rejection most of the infiltrating lymphocytes display the slow mobility of (resting) B cells. The blast response follows 2 days after the influx of lymphocytes. The (B) plasmablast response takes place somewhat earlier and is higher in magnitude than the (T) lymphoblast response. Macrophages appear 1.5 days after the influx of monocytes. The inflammatory cells proliferate rapidly: after 1 h of pulse-labelling with 3H-TdR in vivo up to 24% of the infiltrating leucocytes are labelled. Most labelled cells are blast cells or lymphocytes, although a small but distinct population of labelled monocytes is also detected in situ. The in situ blast and proliferative responses precede the corresponding responses in the host central lymphatic system, i.e. spleen, blood and lymph nodes. The inflammatory leucocytes are isolated from the allograft parenchymal cells via 1 g velocity sedimentation. They are strongly and specifically cytotoxic in the 6 h 51Cr release assay to donor-derived lymphoid target cells in vitro. The peak in situ cytotoxic activity in the graft takes place already on day 5 after the transplantation, whereas in the central lymphatic system the cytotoxic cells are detected later and peak values are obtained only after the activity in situ has declined. The findings emphasize the role of the graft as the site of sensitization of kidney transplantation (peripheral sensitization) and the complex nature of the inflammatory response responsible for allograft rejection.
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D002455:Cell Division; D002469:Cell Separation; D003601:Cytotoxicity Tests, Immunologic; D004586:Electrophoresis; D006084:Graft Rejection; D016030:Kidney Transplantation; D007694:Killer Cells, Natural / Q000276:immunology*; D007958:Leukocyte Count; D007962:Leukocytes / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology; D009000:Monocytes / Q000276:immunology; D051381:Rats; D011919:Rats, Inbred Strains; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous