In vivo migration of lymphocytes in chronically rejecting rat kidney allografts

Histological analyses have identified lymphocytes and macrophages as the pr edominant leukocyte populations that infiltrate organs undergoing chronic r ejection. In order to define the time frame of this infiltration, we invest igated the in vivo migration pattern of lymphocytes in a well-established r at model of chronic kidney allograft rejection. F344 kidneys were orthotopi cally transplanted into bilaterally nephrectomized Lewis rats. Recipients w ere treated with cyclosporin A (1.5 mg/kg/per day) for the first 10 days. A fter anti-CD18 or vehicle pretreatment, peripheral blood lymphocytes obtain ed from naive Lewis rats and labeled with 3H-uridine were injected into tra nsplanted rats 12 and 16 weeks after transplantation. Organs were harvested 4, 8, and 12 h thereafter. After 12 weeks, proteinuria developed, accompan ied by all signs of chronic rejection including glomerular sclerosis. Label ed lymphocytes rapidly infiltrated grafted kidneys 4 h after injection. Eve n more lymphocytes had accumulated in the grafts 12 h after injection. Afte r 16 weeks, few lymphocytes had emigrated into the graft at 4 h, while infi ltration was most pronounced by 12 h. Pretreatment with anti-CD18 inhibited the influx of lymphocytes. There was no difference between the patterns of lymphocytes derived from naive and transplanted rats. Our results emphasiz e the importance of endothelial cells in chronically rejecting kidneys for the control of leukocyte influx. beta 2-integrins may play a central role i n determining the transendothelial migration during this process.