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* Instituto de Biologia Molecular e Celular, Porto, Portugal;
Instituto de Ciências Biomédicas Abel Salazar, Porto, Portugal;
Centro de Investigação em Ciências da Saúde, Instituto Superior de Ciências da Saúde-Norte (ISCSN), Cooperativa de Ensino Superior Politécnico Universitário (CESPU), Portugal; and
University Clinic of Düsseldorf, Institute for Transplantation Diagnostics and Cell Therapeutics, Düsseldorf, Germany
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.
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1 This work was supported by grants from the American Portuguese Biomedical Research Fund (Inova Grant) and from ISCSN-CESPU (Grants CESPU 1F/05/2005 and CESPU 2F/03/2006). M.P.C. was supported by a fellowship from Fundação para a Ciência e a Tecnologia (SFRH/BD/24396/2005).
2 Current address: Lymphocyte Development Group, Medical Research Council Clinical Sciences Centre, London, U.K.
3 Address correspondence and reprint requests to Dr. Fernando A. Arosa, Instituto de Biologia Molecular e Celular, Lymphocyte Biology Group, Rua do Campo Alegre, 823, 4150-180 Porto, Portugal. E-mail address: farosa{at}ibmc.up.pt
4 Abbreviations used in this paper: KIR, killer Ig-like receptor; APS, amphotericin B/penicillin/streptomycin; CM, conditioned medium; FBSi, inactivated FBS; FSC, forward light scatter; IHH, immortalized human hepatocyte; PI, propidium iodide; SSC, side light scatter.
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