Hepatocytes and IL-15: A favorable microenvironment for T cell survival and CD8+ T cell differentiation

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Human intrahepatic lymphocytes are enriched in CD1d-unrestricted T cells coexpressing NKR. Although the origin of this population remains controversial, it is possible to speculate that the hepatic microenvironment, namely epithelial cells or the cytokine milieu, may play a role in its shaping. IL-15 is constitutively expressed in the liver and has a key role in activation and survival of innate and tissue-associated immune cells. In this in vitro study, we examined whether hepatocyte cell lines and/or IL-15 could play a role in the generation of NK-like T cells. The results show that both HepG2 cells and a human immortalized hepatocyte cell line increase survival and drive basal proliferation of T cells. In addition, IL-15 was capable of inducing Ag-independent up-regulation of NKR, including NKG2A, Ig-like receptors, and de novo expression of CD56 and NKp46 in CD8+CD56- T cells. In conclusion, our study suggests that hepatocytes and IL-15 create a favorable microenvironment for T cells to growth and survive. It can be proposed that the increased percentage of intrahepatic nonclassical NKT cells could be in part due to a local CD8+ T cell differentiation.


  • Margareta P. Correia
  • Elsa M. Cardoso
  • Carlos F. Pereira
  • Rui Neves
  • Markus Uhrberg
  • Fernando A. Arosa
External organisations
  • University of Porto
  • Instituto Superior de Ciências da Saúde - Norte (CESPU)
  • Lymphocyte Development Group, London Institue of Medical Sciences
  • MRC Human Nutrition Research
  • Universitätsklinikum Düsseldorf
  • Instituto de Biologia Molecular e Celular
Original languageEnglish
Pages (from-to)6149-6159
Number of pages11
JournalJournal of Immunology
Issue number10
Publication statusPublished - 2009 May 15
Publication categoryResearch
Externally publishedYes