| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥6,500,000)
Fiscal Year 1992: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1991: ¥4,700,000 (Direct Cost: ¥4,700,000)
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| Research Abstract |
Recently, we reported that hepatic allografts are permanently accepted when transplanted following IP of donor SPCs. Although this immunosuppressive effect is well known, the mechanisms involved are not understood yet. In order to clarify them, from the viewpoint of injected antigen accumulation in the liver, the immunosuppressive effect was investigated in relation to antigen accumulation following different treatments of antigen injection. ACI(RT1a) and Buffalo(RT1b) rats were used as donors and recipients, respectively. Experimental groups were divided into the following groups depending on the treatment: IP,IV,Spx and IV+Spx. The accumulation ratio examined by injecting ^<51>Cr-labelled SPCs in the liver was significantly higher in the IP and IV+Spx groups than the IV group (p<0.05). DTH responses (x10^<-2>mm) as cellular response were lower in IP and IV+Spx groups than in the IV or Spx groups (p<0.05). CDC titer (log2) as humoral response at 7 days postinoculation was significantl
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y lower in the IP and IV+Spx groups than in the IV group (p<0.05). In order to examine whether the treatment actively suppress the immune response, rechallenging of SPCs by the IV route was performed 10 days after inoculation. Elevation of CDC titer was suppressed in the IP and IV+Spx groups, but not in the IV and Spx groups, (p<0.05). The survival of hepatic allografts in the IV group tended to be shorter. No significant prolongation of the graft survival was observed in the Spx group. In contrast, all hepatic allotransplants in IP and IV+Spx groups survived over 45 days.
In conclusion, the animals in which donor SPCs were injected intraportally or intravenously after splenectomy showed high accumulation of donor SPCs in the liver followed by suppression of DTH and CDC antibody production, with the finally being accepted liver allografts. These findings suggest that the accumulation of donor SPCs in the liver rather than the difference of inoculation route may play an important role in inducing immunosuppression following intraportal injection of donor SPCs.
SPCs:Spleen cells,IP:intraportal injection, IV:intravenous injection,
Spx:splenectomy,IV+Spx:intravenousinjection following splenectomy Less
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