CD4 T-cell regulation of cytotoxic T cells during the induction phase of liver-induced spontaneous tolerance in rats.

ABSTRACT

PURPOSE: To check for in vivo CD4 T-cell-mediated inhibition of the immune response in rats with spontaneously accepted liver transplants. METHODS: Using the Lewis to Wistar Furth rat strain combination, we performed transient in vivo depletion of CD4 T-cells by anti-CD4 monoclonal antibodies (mAb) after liver transplantation. We used the CTL assay to detect primed T cells. We also retransplanted a grafted donor liver, parked for 3 days, into a secondary naive recipient rat. RESULTS: When Lewis rat livers were transplanted into the recipient Wistar Furth rats, the grafts suffered an early immune attack, followed by spontaneous acceptance without immunosuppression. However, giving anti-CD4 mAb to the recipients at the time of grafting prolonged the acute rejection reaction. Furthermore, giving anti-CD4 therapy on postoperative days (PODs) 21 and 35, but not on PODs 56 and 100, induced transient liver damage in recipients overcoming acute rejection. No primed T cells were detected by the CTL assay in the recipient rats within 2 months after transplantation. Meanwhile, the retransplanted liver had no ability to elicit an immune attack. CONCLUSIONS: CD4 T cells seemed to downregulate the effector function of T cells, but not T-cell proliferation in this model.