Abstracts
1997 Digestive Disease Week

Effect of anti-ICAM-1 and anti-LFA-1 monoclonal antibodies in experimental islet transplantation.

K Arai, M Sunamura, K Amikura, M Kobari, S Matsuno. First Department of Surgery, Tohoku University School of Medicine, Sendai, Japan.

ICAM-1 and LFA-1 are known to play a critical role in graft rejection. We examined the immunosuppressive effect of anti-ICAM-1 and anti-LFA-1 mAbs in experimantal islet allo- and xenotransplantation.

[Materials and Methods] 500 isoleted islets from ICR mice or Lewis rats were transplanted into the renal subcapsular space of streptozotocin-induced diabetic C57BL/6 mice. MAbs to ICAM-1 and/or LFA-1 were administered from day 0 to 6. In mice with allograft, intragraft expression of cytokine transcripts was analyzed by RT-PCR.

[Results] 1) Allograft Survival: Treatment with mAbs significantly prolonged graft survival comparing with graft survival in nontreated mice. Mean survival time of each group was the following: no treatment = 10.0±2.9 days, anti-mouse ICAM-1 mAb alone = >49.4±38.1 days (P<0.01), anti-mouse LFA-1 mAb alone = >78.2±34.6 days (P<0.001), and combination of both mAbs = >91.3±24.7 days (P<0.001). Combination of anti-ICAM-1/LFA-1 mAbs induced indefinite graft survival over 100 days in 88% of recipients. 2) Xenograft Survival: Combination treatment of anti-rat ICAM-1, anti-mouse ICAM-1 and anti-mouse LFA-1 mAbs resulted in significant prolongation of rat islet xenografts (MST: 54.4±33.0 vs. 12.7±2.2 days for nontreated control, P<0.01). However, long-term survival over 100 days was observed in only 29% of recipients with the mAbs treatment. 3) Intragraft expression of cytokine transcripts in mice with allograft: Th1 cytokine (IL-2 and IFN-gamma) transdripts were detected and Th2 cytokine (IL-4 and IL-10) transdripts were not expressed in nontreated mice. In contrast, Th2 cytokines were expressed and Th1 cytokine transdripts were not detected in treated mice with anti-ICAM-1/LFA-1 mAbs.

[Conclusion] 1) Short-term administration of anti-ICAM-1 and anti-LFA-1 mAbs can induce indefinite graft survival in islet allotransplantation and it may be associated with the lack of Th1 cytokines and Th2 activation. 2) Blockade of ICAM-1 and LFA-1 also prolongs graft survival in xenotransplantation but it is less effective than that in allotransplantation.