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. 2009 Oct;54(10):2253-63.
doi: 10.1007/s10620-008-0618-y. Epub 2008 Dec 11.

Impact of preexisting circulating effector T cells on the outcome of ABO-incompatible adult LDLT

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Impact of preexisting circulating effector T cells on the outcome of ABO-incompatible adult LDLT

Hiroto Egawa et al. Dig Dis Sci. 2009 Oct.

Abstract

Our aim was to clarify the significance of phenotype of circulating CD8 T(+) cells on the outcome of ABO-incompatible (ABO-I) living donor liver transplantation (LDLT). Twenty-six recipients undergoing ABO-I LDLT and 92 undergoing ABO-compatible (ABO-C) LDLT were classified into three groups according to preoperative proportion of CD8 T(+) cells: naive-dominant (group I), effector memory-dominant (group II), and effector-dominant (group III) recipients. The clinical courses were analyzed. The results showed that in ABO-C groups I and II and in ABO-I group I, effector cells remained above the pretransplant levels after tacrolimus administration. However, in ABO-C group III and ABO-I groups II and III, effector cells were down-regulated for a prolonged period, along with markedly decreased perforin expression and frequent life-threatening complications. ABO-I group II and group III recipients had higher infection rates. It was concluded that recipients with preexisting high effector CD8 T(+) cells are unfavorable candidates for ABO-I LDLT.

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Figures

Fig. 1
Fig. 1
The scheme of immunosuppression regimen and the changes in trough levels of tacrolimus after LDLT in ABO-C and ABO-I recipients. a For a recipient of ABO-I LDLT, rituximab was administered once at a dose of 375 mg/m2 as prophylaxis before transplantation. PEX was performed, aiming for an antibody titer 8-fold less before transplantation. Local infusion therapy was continued for 3 weeks. Intravenous cyclophosphamide was administered for 2 weeks at a dose of 2 mg/kg/day and then MMF was administered (500 mg twice/day). MMF was continued for 1 year after transplantation. Basic immunosuppression consisting of tacrolimus and corticosteroids was the same for ABO-C LDLT. b There was no significant differences in trough levels of tacrolimus between ABO-C and ABO-I recipients. LDLT, living donor liver transplantation; HAI, hepatic artery infusion; PVI, portal vein infusion; PGE1, prostaglandin E1; PEX, plasmapheresis
Fig. 2
Fig. 2
Changes in the proportion (top) and the difference (bottom) of CD8+ effector T cells after LDLT in 3 groups of ABO-C and ABO-I recipients. % E difference refers to % difference of CD8+ effector T cells. LDLT, living donor liver transplantation
Fig. 3
Fig. 3
Changes in the % difference of perforin in CD8+ effector T cells after LDLT in three groups of ABO-C and ABO-I recipients. a The proportion of perforin expression is expressed as % of CD8+ T cells. b Flow cytometry of representative ABO-C and ABO-I group III recipients. Dot plots show double staining for perforin/CCR7. Perforin/CCR7 was gated on CD8+CD45RO. Cells in the upper left are presented as %. Tac, tacrolimus; LDLT, living donor liver transplantation
Fig. 4
Fig. 4
The frequencies of infection, ACR, LTCs, and hospital mortality after ABO-C LDLT and ABO-I LDLT. White bars show ABO-C LDLT, dark bars ABO-I LDLT. ACR, acute cellular rejection; LTC, life-threatening complication; LDLT, living donor liver transplantation

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