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P100 Liver transplantation (LT) results in reduced recipient Natural Killer (NK) cell activation with associated down regulation of activating receptors NKp30 and NKp46 but not NKG2D
  1. K M Jamil1,
  2. K S Cheent1,
  3. K Agarwal2,
  4. G J Alexander3,
  5. M A Heneghan2,
  6. S I Khakoo1
  1. 1Imperial College London
  2. 2King's College Hospital, London
  3. 3Addenbrookes Hospital, Cambridge

Abstract

Introduction In solid organ transplantation, the effect of the allograft on recipient NK cell function is poorly understood. NK cells recognise self through inhibitory receptors for HLA class I, so that they lyse target cells that do not express self HLA class I molecules (the “missing-self” model). As liver transplants are not matched for HLA, significant NK cell alloreactivity is expected, but is not seen in practise.

Aim This aim of this study is to investigate the effect of LT on recipient NK cell reactivity.

Method Whole blood was collected from 16 liver transplant patients and 10 controls. The transplant patients were all on calcineurin inhibitor-based immunosuppression. NK cells from the peripheral blood were analysed for expression of the cell surface inhibitory receptors CD158a/b (killer cell immunoglobulin-like receptors (KIR) specific for HLA-C), and the activating receptors NKp30, NKp46 and NKG2D. Following overnight incubation with IL-15 NK cell function was assessed using a flow cytometry-based killing assay.

Results There was significantly reduced expression of NKp30 and NKp46 in post LT patients compared with controls (p<0.001 for both, Student t test), but no reduction in NKG2D expression (Abstract P100 figure 1). There was no difference in KIR expression or segregation of activating receptor expression with expression of specific KIR. However, consistent with the phenotyping results there was a significant reduction of NK cell killing of target cells in post LT patients compared with controls as shown in Abstract P100 figure 2 (p=0.011, Student t test).

Abstract P100 Figure 1

Expression of activating receptors on NK cells.

Abstract P100 Figure 2

NK cell Killing of K562 target cells.

Conclusion Following liver transplantation there is down-regulation of activating NK cell receptors and suppression of NK cell activity. We propose that this suppression helps to maintain tolerance of the HLA-mismatched liver allograft.

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