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Abstract
Although the administration of donor lymphocytes via portal vein (PV) on the day of transplantation significantly prolongs rat renal allograft survivals and the unresponsive state is mediated by an antigen-specific suppressor factor in the serum, significant variations exist among rodent models in terms of immunogenecity and mechanism of antigen presentation. The present studies sought to assess the effect of perioperative PV inoculation with donor lymphocytes on skin allograft survivals. Donor lymphocytes were prepared from Brown-Norway (BN, RT-1a) or third-party DA (RT-1a) rat spleens and lymph nodes and injected via PV or intravenously to Lewis (LEW, RT-11) hosts on the day of skin grafting. Untreated LEW hosts rejected BN skin grafts at 9.0 ± 1.4 days (n= 10). Intravenous administration of 1 ± 108 BN cells into LEW hosts on day 0 did not prolong the skin graft survivals (MST= 8.6 ± 1.2 days, n= 7, NS), whereas PV inoculation of 1 × 108 BN cells prolonged skin graft survival to 13.4 ± 3.9 (n= 8, P <. 01). PV administration of 1 × 108 DA cells to LEW hosts did not prolong the survival of BN skin grafts (MST= 8.6 ± 1.5 days, n= 6). PV inoculation with BN cells inhibited the generation of anti-BN delayed-type hypersensitivity (DTH) response in the hosts, whereas untreated control hosts or hosts inoculated with third-party DA cells could not inhibit the anti-BN DTH response. When serum harvested from PV-treated LEW hosts on day 7 was added to MLC, it suppressed the reaction toward donor BN cells by 61%, but not toward third-party DA stimulators (4.8% suppression, NS). Moreover, adoptive transfer of the serum from PV-treated LEW rats into the virgin secondary LEW hosts significantly prolonged the graft survivals of BN kidney from 7.8 to 16.3 ±1.1 days (n= 6, P ≤. 01), but not third-party DA renal graft (MST= 7.7 ± 0.5, n= 8, NS) or BN skin graft (MST= 9.8 ± 1.2 days, n= 5, NS). These studies suggest that the suppressor mechanism demonstrated in the PV-treated renal transplant model might be similarly active in the hosts who received skin grafts simultaneously with the PV inoculation of donor cells.