Intragraft gene and protein expression in rat liver allografts treated with costimulatory blockade alone or in combination with CyA
In: Journal of Surgical Research, Jg. 115 (2003-11-01), Heft 1, S. 1-8
academicJournal
Zugriff:
Background. Costimulatory blockade has been shown to prevent acute rejection (AR) and promote long-term graft survival in a number of animal models including nonhuman primates. The effect of concomitant administration of conventional immunosuppressives on long-term liver allograft survival and intragraft expression of immune mediators has not previously been examined.Materials and methods. A high-responding Dark Agouti to Lewis orthotopic liver transplant (LEW OLT) model was used to compare anti-CD154 alone, or in combination with cyclosporin (CyA) on allograft survival. Donor-specific reactivity was assessed by mixed lymphocyte reaction (MLR) and allogeneic skin grafts. Surviving rats were euthanized on day 150 and intragraft gene (CD80, 86, 152, 154, IFN-γ, IL-2, IL-6, IL-10, IL-13, TNF-α, TGF-β, IL-7, Fas-ligand, Granzyme B, bax, and bcl2) and protein (CD4, CD8, ED1, CD154, CD80, CD86) expression was measured.Results. Untreated control recipients had a median survival time of 5 days. Recipients treated with anti-CD154 survived to beyond 150 days with no evidence of AR. Concomitant administration of CyA did not alter the long-term survival. There was no difference in the serum aspartate aminotransferase between treatment groups or a change over time. All treated recipients showed a reduction in donor-specific MLR at day 40 and 60 but had persistence of donor reactivity to skin grafts at day 100. Histologically, liver architecture was well preserved despite the presence of a nondestructive mononuclear cell infiltrate. Analysis of intragraft gene expression revealed an inverse relationship between the duration of anti-CD154 therapy and the gene expression of costimulatory molecules and Th1 cytokine transcripts. The pro-apoptotic gene, bax, was increased in recipients treated with anti-CD154, but not CyA, compared with normal liver.Conclusions. These data demonstrate that anti-CD154 therapy either alone or in combination with CyA allows for the long-term survival of liver allografts in the rat despite there being a difference in the intragraft gene and protein profile. [Copyright &y& Elsevier]
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Intragraft gene and protein expression in rat liver allografts treated with costimulatory blockade alone or in combination with CyA
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Autor/in / Beteiligte Person: | Bartlett, Adam S.R. ; McCall, John L. ; Ameratunga, Rohan ; Howden, Brian ; Ramadas, Ravi ; Yeong, Mee-Ling ; Benjamin, Christopher D. ; Hess, Donna ; Munn, Stephen R. |
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Zeitschrift: | Journal of Surgical Research, Jg. 115 (2003-11-01), Heft 1, S. 1-8 |
Veröffentlichung: | 2003 |
Medientyp: | academicJournal |
ISSN: | 0022-4804 (print) |
DOI: | 10.1016/S0022-4804(03)00131-8 |
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