Timing of lymphocyte transfusion and portal clamping for the development of lethal graft-versus-host disease in the rat.

The effects of surgical intervention on the incidence and augmentation of graft-versus-host disease (GVHD) were studied in the rat. To elicit GVHD, splenocytes from parental LEW rats at a dose of 4 x 10(8) or 1.5 x 10(8) cells/350g body weight were injected via the tail vein into (LEW x BN)F1 rats. The injection of 4 x 10(8) of LEW rat splenocytes induced lethal GVHD in all nontreated F1 rats, while 1.5 x 10(8) of LEW splenocytes did not induce any signs of GVHD. However, when the F1 rats had received the same dose of parental LEW lymphocytes in combination with portal clamping, 14 recipients out of the 15 rats (93%) suffered GVHD and 10 rats (67%) died from GVHD. Interestingly, portal clamping 7 days after the injection enhanced the incidence of GVHD, whereas no GVHD was observed in the intervention group either 3 or 7 days prior to the cell transfusion. When 1.5 x 10(8) of allogeneic lymphocytes were injected intravenously together with 0.1-1.0 mg/kg of endotoxin instead of portal clamping, the injection led the early death by GVHD, while the injection of methylpredonisolone did not enhance GVHD. These results thus indicate that either simultaneous or delayed surgical intervention has the potential to trigger a dormant state in transferred alloreactive lymphocytes.