Hepatocytes and IL-15: a favorable microenvironment for T cell survival and CD8+ T cell differentiation.
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.
Instituto de Biologia Molecular e Celular, Porto, Portugal.
Margareta P
MP
Correia
Elsa M
EM
Cardoso
Carlos F
CF
Pereira
Rui
R
Neves
Markus
M
Uhrberg
Fernando A
FA
Arosa
D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology*; D002460:Cell Line; D002470:Cell Survival / Q000276:immunology*; D018920:Coculture Techniques; D005434:Flow Cytometry; D022781:Hepatocytes / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D019409:Interleukin-15 / Q000276:immunology* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
D019409:Interleukin-15