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 elici t 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)F-1 rats. The injection of 4 x 108 of LEW rat splenocytes i nduced lethal GVHD in all nontreated F-1 rats, while 1.5 x 10(8) of LE W splenocytes did not induce any signs of GVHD. However, when the F-1 rats had received the same dose of parental LEW lymphocytes in combina tion with portal clamping, 14 recipients out of the 15 rats (93%) suff ered GVHD and 10 rats (67%) died from GVHD. Interestingly, portal clam ping 7 days after the injection enhanced the incidence of GVHD, wherea s no GVHD was observed in the intervention group either 3 or 7 days pr ior to the cell transfusion. When 1.5 x 10(8) of allogeneic lymphocyte s were injected intravenously togather 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. The se results thus indicate that either simultaneous or delayed surgical intervention has the potential to trigger a dormant state in transferr ed alloreactive lymphocytes.