Abstract
Background. Transplant arteriosclerosis is a major limiting factor for long-term function of allografts in clinical transplantation. This study investigated the impact of three different protocols capable of inducing long-term allograft survival on the development of transplant arteriosclerosis and immune response in cardiac allografts. Methods. CBA.Ca (H2k) recipients of fully allogeneic C57/BL10 (H2b) heart grafts received a short-term course of anti-CD154 antibody or were pretreated with anti-CD4 antibody in combination with donor alloantigen in the form of CBK (H2 k+Kb) bone marrow or C57BL/10 donor-specific transfusion (DST). Grafts were analyzed on day 40 or 100 after transplantation for transplant arteriosclerosis and expression of interferon-γ, interleukin (IL)-2, IL-4, IL-10, IL-12p40, inducible nitric oxide synthase, and transforming growth factor (TGF)-β1 mRNA. Serum was analyzed for the presence of alloantibodies. Results. Intimal proliferation was 62%±11% on day 40 in the anti-CD154 group, progressed from 31%±10% on day 40 to 68%±8% on day 100 in the CBK-bone marrow group, but remained stable at 39%±4% in the DST group. Increased transplant arteriosclerosis on day 100 was associated with high intragraft TGF-β1 mRNA production and eosinophil infiltration, but not alloantibody production. Progressing transplant arteriosclerosis was associated with increased IL-4 expression. Conclusion. Treatment protocols for the induction of long-term allograft survival can differ substantially in the extent and kinetics of transplant arteriosclerosis. IL-4 and TGF-β1 may be two potential therapeutic targets to attenuate the development of transplant arteriosclerosis in the long term.
Original language | English |
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Journal | Transplantation |
Volume | 76 |
Issue number | 7 |
Pages (from-to) | 1105-1111 |
Number of pages | 7 |
ISSN | 0041-1337 |
Publication status | Published - 15.10.2003 |