Control of humoral and cellular immunity-mediated accelerated heart allograft rejection in sensitized rats by low dose FK 506 and splenectomy
ACI heart grafts are rejected, at an accelerated pace, in Lewis (LEW) rats sensitized by donor-type blood admixed with immunoadjuvant (adjuvant complete Freund, ACF) 7 days earlier. In an in vitro study, the anti-ACI cytotoxic antibody titers in the serum increased from 1:4 in nonsensitized rats to 1:128 in sensitized rats; the spontaneous blastogenesis in spleen cells was higher in sensitized rats than in nonsensitized rats; spleen cells from sensitized rats showed a strong proliferative response against donor strain stimulator cells compared with the control; the cytotoxic T cell activity of spleen cells from sensitized rats was higher than that of spleen cells from nonsensitized rats. Treatment with low dose FK 506 in combination with splenectomy (Spx) synergistically prolonged the heart allograft survival in this sensitized rat model. In conclusion: (1) Both humoral and cellular responses against the donor antigen appear in the serum and in the spleen of rats sensitized by donor-type blood admixed with immunoadjuvant ACF. (2) A low dose of FK 506 together with Spx appears to control this sensitization through different mechanisms, resulting in a prolongation of heart allograft survival.
Key wordsHeart allograft survival Humoral and cellular immunity FK 506 Splenectomy
Unable to display preview. Download preview PDF.
- 4.Kupiec-Weglinski JW, Sablinski T, Hancock WW, Stefano RD, Mariani G, Mix CT, Tilney NL (1991) Modulation of accelerated rejection of cardiac allografts in sensitized rats by anti-interleukin 2 receptor monoclonal antibody and cyclosporine therapy. Transplantation 51:300–305PubMedCrossRefGoogle Scholar