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Mechanisms of tolerance induction after rat liver transplantation: Intrahepatic CD4+ T cells produce different cytokines during rejection and tolerance in response to stimulation

  • Published:
Journal of Gastrointestinal Surgery

Abstract

Increasing evidence supports the existence of regulatory T cells that may inhibit the allogeneic immune response after transplantation by secreting regulatory cytokines. To determine whether rat liver tolerance is associated with intrahepatic regulatory T cells secreting a characteristic cytokine profile, we analyzed the cytokine production of freshly isolated intragraft CD4+ T cells at different times postoperatively by semiquantitative reverse transcription-polymerase chain reaction and by enzyme-linked immunosorbent assay before and after in vitro stimulation. Orthotopic arterialized liver transplantation was performed in two allogeneic rat strain combinations, one with fatal acute rejection (DA-to-LEW) and one with long-lasting tolerance (LEW-to-DA) without immunosuppression despite a complete major histocompatibility complex mismatch (spontaneous liver tolerance). Liver allografts of both groups showed continuously increasing cellular infiltration between day 3 and day 7 after transplantation. In this inflammatory situation, very low levels of interleukin-13 were detectable directly after cell isolation, as well as after in vitro stimulation. However, after 30 days, intrahepatic CD4+T cells in the tolerance group were then able to express elevated messenger RNA levels of the anti-inflammatory cytokine interleukin-13 in response to stimulation. This result indicates the presence of an intragraft Th2-like CD4+T cell population, which may have a regulatory function in the induction of liver tolerance.

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Authors and Affiliations

  1. Experimental Transplantation Immunology Unit of the Department of Surgery, University of Würzburg, Würzburg, Germany

    Jens Kauczok M.D., Natascha Martens, Ulrich Steger M.D., Ingo Möller M.D. & Karin Ulrichs Ph.D.

  2. Department of Surgery, University of Würzburg, Würzburg, Germany

    Detlef Meyer M.D., Wolfgang Timmermann M.D. & Heinz-Jochen Gassel M.D.

  3. Department of Surgery (Director: Prof. Dr. med. A. Thiede), Experimental Transplantation Immunology Unit of the Department of Surgery, University of Würzburg, Josef-Schneider-Str. 2, D-97080, Würzburg, Germany

    Christoph Otto Ph.D.

Authors
  1. Christoph Otto Ph.D.
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  2. Jens Kauczok M.D.
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  3. Natascha Martens
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  4. Ulrich Steger M.D.
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  5. Ingo Möller M.D.
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  6. Detlef Meyer M.D.
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  7. Wolfgang Timmermann M.D.
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  8. Karin Ulrichs Ph.D.
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  9. Heinz-Jochen Gassel M.D.
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Correspondence to Christoph Otto Ph.D..

Additional information

Supported by the Federal Ministry of Education and by research funds supplied to the Interdisciplinary Centre for Clinical Research (IZKF) of the University of Würzburg (research project grant number 01 KS 9603).

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Otto, C., Kauczok, J., Martens, N. et al. Mechanisms of tolerance induction after rat liver transplantation: Intrahepatic CD4+ T cells produce different cytokines during rejection and tolerance in response to stimulation. J Gastrointest Surg 6, 455–463 (2002). https://doi.org/10.1016/S1091-255X(02)00012-4

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  • DOI: https://doi.org/10.1016/S1091-255X(02)00012-4

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