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Liver grafts contain a unique subset of natural killer cells that are transferred into the recipient after liver transplantation

  1. Viviana Moroso1,
  2. Herold J. Metselaar1,
  3. Shanta Mancham1,
  4. Hugo W. Tilanus2,
  5. Diana Eissens3,
  6. Arnold van der Meer3,
  7. Luc J. W. van der Laan2,
  8. Ernst J. Kuipers1,
  9. Irma Joosten3,
  10. Jaap Kwekkeboom1,†,*

Article first published online: 6 APR 2010

DOI: 10.1002/lt.22080

Issue

Liver Transplantation

Liver Transplantation

Volume 16, Issue 7, pages 895–908, July 2010

Additional Information

How to Cite

Moroso, V., Metselaar, H. J., Mancham, S., Tilanus, H. W., Eissens, D., van der Meer, A., van der Laan, L. J. W., Kuipers, E. J., Joosten, I. and Kwekkeboom, J. (2010), Liver grafts contain a unique subset of natural killer cells that are transferred into the recipient after liver transplantation. Liver Transpl, 16: 895–908. doi: 10.1002/lt.22080

Author Information

  1. 1

    Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands

  2. 2

    Surgery, Erasmus MC University Medical Center, Rotterdam, The Netherlands

  3. 3

    Department of Laboratory Medicine–Laboratory of Medical Immunology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands

  1. †

    Telephone: 31-10-7034776; FAX: 31-10-7032793

*Laboratory of Gastroenterology and Hepatology, Room L-455, Erasmus MC, s-Gravendijkwal 230, 3015 GD Rotterdam, The Netherlands

  1. †

    Telephone: 31-10-7034776; FAX: 31-10-7032793

Publication History

  1. Issue published online: 25 JUN 2010
  2. Article first published online: 6 APR 2010
  3. Manuscript Accepted: 28 MAR 2010
  4. Manuscript Received: 23 DEC 2009

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Abstract

In contrast to other solid organ transplantations, liver grafts have tolerogenic properties. Animal models indicate that donor leukocytes transferred into the recipient after liver transplantation (LTX) play a relevant role in this tolerogenic phenomenon. However, the specific donor cell types involved in modulation of the recipient alloresponse are not yet defined. We hypothesized that this unique property of liver grafts may be related to their high content of organ-specific natural killer (NK) and CD56+ T cells. Here, we show that a high proportion of hepatic NK cells that detach from human liver grafts during pretransplant perfusion belong to the CD56bright subset, and are in an activated state (CD69+). Liver NK cells contained perforin and granzymes, exerted stronger cytotoxicity against K562 target cells when compared with blood NK cells, and secreted interferon-γ, but no interleukin-10 or T helper 2 cytokines, upon stimulation with monokines. Interestingly, whereas the CD56bright subset is classically considered as noncytolytic, liver CD56bright NK cells showed a high content of cytolytic molecules and degranulated in response to K562 cells. After LTX, but not after renal transplantation, significant numbers of donor CD56dim NK and CD56+ T cells were detected in the recipient circulation for approximately 2 weeks. In conclusion, during clinical LTX, activated and highly cytotoxic NK cells of donor origin are transferred into the recipient, and a subset of them mixes with the recirculating recipient NK cell pool. The unique properties of the transferred hepatic NK cells may enable them to play a role in regulating the immunological response of the recipient against the graft and therefore contribute to liver tolerogenicity. Liver Transpl 16:895–908, 2010. © 2010 AASLD.

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