Shigeki Hikida

Inhibition of Acute Rejection After Skin or Cardiac Transplantation by Administration of Donor Antigens in the Rat

PurposeWe examined differences in host immunologic changes induced by the intravenous or intraportal administration of donor antigens at engrafting and evaluated their contribution to graft survival using a rat transplantation model.MethodsLewis rat recipients were given either an intravenous or intraportal injection of donor splenocytes (1 × 108) immediately after receiving skin grafts from Brown Norway donors. The immunologic responses were analyzed by mixed lymphocyte reaction (MLR) and profiles of interferon-Γ, interleukin (IL)-2, and IL-10 in MLR supernatants. The effect on cardiac transplantation of perioperative administration of low-dose FK506 (0.1 mg/kg per day) was also examined.ResultsMixed lymphocyte reactions using splenocytes and sera from recipients treated intraportally were greatly inhibited. Interferon-Γ, IL-2, and IL-10 levels were significantly higher after intraportal treatment compared with intravenous treatment (P ≪ 0.05). When FK506 was injected from day 3, a significant enhancement of cardiac allograft survival was demonstrated by intraportal treatment (16.1 ± 2.9 days) in comparison to the non-treatment (13.0 ± 1.7 days, P ≪ 0.05) and intravenous treatment rats (11.7 ± 2.7 days, P ≪ 0.05).ConclusionsThe Th2 deviation induced with intraportal alloantigen administration immediately after engraftment was thus observed to produce a synergistic effect with immunosuppressant treatment to suppress acute rejection.

Extracellular Ca2+ uptake by T cells might help to make a diagnosis of acute rejection

To more non-invasively diagnose acute rejection, we focused on the uptake of extracellular Ca2+ by T cells as a result of the activation of Ca2+ release activated Ca2+ channels. A full thickness of the skin allograft model was established using BN rats as the donors and LEW rats as the recipients, and similar LEW rats as both donors and recipients in the control group. After transplantation, the grafts were staged histopathologically in both rats. The uptake of extaracellular 45Ca pre T cell was measured in the macrophage-treated and non-treated groups, and the ratios between the two groups were calculated and the results were compared according to the post-operative day. No histopathological findings of acute rejection were observed in the control group. The allograft model group showed acute rejection histopathologically beginning on day 2 and increased through day 5. The macrophage-treated model/non-treated model 45Ca uptake ratio (CAR) was significantly higher in the allograft rats on day 2. No significant difference was observed on day 4. Measuring the uptake of extracellular Ca2+ by recipient T cells using donor macrophages might be useful for making a diagnosis of acute rejection.