Abstract
Interferon-γ is a key immunoregulatory cytokine involved in acute graft rejection. Immunologic unresponsiveness to organ allografts has been induced by pretransplantation donor-specific blood transfusion, both experimentally and clinically. We investigated interferon-γ production and intragraft gene expression of type-1 T-helper cytokines such as interleukin-12 and -18 and type-2 T-helper cytokines such as interleukin-10 and transforming growth factor-β in rats receiving hepatic allografts after such transfusions. The animals were divided into four groups: group I received isografts; group II received allografts; group III received allografts after donor-specific transfusion; and group IV received allografts and was treated with FK 506. Donor blood given seven days prior to transplantation significantly prolonged allograft survival. The serum interferon-γ concentrations in group II increased, peaking on day 5 and then decreasing. Serum interferon-γ concentrations in groups I, III, and IV were significantly lower than those observed in group II, as were levels of interleukin-12 and interleukin-18 mRNA in the graft. Transforming growth factor-β and interleukin-10 mRNA levels in grafts in transfused animals were significantly greater than those in the untreated allograft group. Interleukin-12 and -18 mRNA transcripts in an allogeneic mixed lymphocyte reaction were inhibited by interleukin-10 and transforming growth factor-β. These results suggest that interleukin-12 and -18 expression in hepatic allografts is inhibited in the immunologically unresponsive state induced by donor-specific transfusion.
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Yamaguchi, Y., Matsumura, F., Liang, J. et al. Reduced Interleukin-12, Interleukin-18, and Interferon-γ Production with Prolonged Rat Hepatic Allograft Survival After Donor-Specific Blood Transfusion. Dig Dis Sci 45, 2429–2435 (2000). https://doi.org/10.1023/A:1005659529472
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DOI: https://doi.org/10.1023/A:1005659529472