Effect of streptavidin on cardiac allograft prolongation is due to host T-Cell suppression

Abstract

Aim The aim of this study was to evaluate the effectiveness of streptavidin immunomodulation in the high-responder WF-to-Lewis combination. Methods/results We examined the effects of streptavidin on the proliferative response of T cells in coculture studies. Two to 200 μg/mL streptavidin significantly ( P < .001) suppressed the proliferation of Lewis T cells to WF by 76%–83% compared with untreated responders. Next, we studied the survival of WF cardiac allografts in Lewis recipients pretreated with streptavidin. A 5-day course of peritransplantation recipient treatment with streptavidin doses of 8, 12, 20, 40, and 60 mg/kg combined with single dose of 0.5 mL antilymphocyte serum (ALS) significantly ( P < .001) prolonged cardiac allograft survival from MST of 7 ± 0.5 and 8 ± 0.5 days in naive and ALS-treated controls to 15 ± 1, 20 ± 3, 16 ± 3, 17 ± 3, and 23 ± 2 days, respectively. In contrast, posttransplantation administration of 80 mg/kg streptavidin resulted in animal death, suggesting toxicity of this dose. Additionally, 10 mg/kg or 20 mg/kg streptavidin administration for 10 consecutive days resulted in significant graft prolongation (MST of 18 ± 1 and 21 ± 1 days, respectively; P < .001). Conclusion Although peritransplantation streptavidin treatment is effective in prolonging rat cardiac allografts in the high-responder WF-to-Lewis combination, it does not induce permanent graft survival as observed in the low-responder combination of Lewis-to-ACI. Our finding of in vitro immunomodulatory effect of streptavidin on T-cell proliferation suggests that its in vivo effect is partly due to prevention of T-cell activation following antigen exposure.