{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T23:57:49Z","timestamp":1769644669707,"version":"3.49.0"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2009,5,1]],"date-time":"2009-05-01T00:00:00Z","timestamp":1241136000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,5,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>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\u2212 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.<\/jats:p>","DOI":"10.4049\/jimmunol.0802470","type":"journal-article","created":{"date-parts":[[2009,5,4]],"date-time":"2009-05-04T16:48:20Z","timestamp":1241455700000},"page":"6149-6159","source":"Crossref","is-referenced-by-count":41,"title":["Hepatocytes and IL-15: A Favorable Microenvironment for T Cell Survival and CD8+ T Cell Differentiation"],"prefix":"10.1093","volume":"182","author":[{"given":"Margareta P","family":"Correia","sequence":"first","affiliation":[{"name":"Instituto de Biologia Molecular e Celular , Porto,","place":["Portugal"]},{"name":"Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar , Porto,","place":["Portugal"]}]},{"given":"Elsa M","family":"Cardoso","sequence":"additional","affiliation":[{"name":"Instituto de Biologia Molecular e Celular , Porto,","place":["Portugal"]},{"name":"Centro de Investiga\u00e7\u00e3o em Ci\u00eancias da Sa\u00fade, Instituto Superior de Ci\u00eancias da Sa\u00fade-Norte (ISCSN), Cooperativa de Ensino Superior Polit\u00e9cnico Universit\u00e1rio (CESPU) ,","place":["Portugal"]}]},{"given":"Carlos F","family":"Pereira","sequence":"additional","affiliation":[{"name":"Instituto de Biologia Molecular e Celular , Porto,","place":["Portugal"]}]},{"given":"Rui","family":"Neves","sequence":"additional","affiliation":[{"name":"University Clinic of D\u00fcsseldorf, Institute for Transplantation Diagnostics and Cell Therapeutics , D\u00fcsseldorf,","place":["Germany"]}]},{"given":"Markus","family":"Uhrberg","sequence":"additional","affiliation":[{"name":"University Clinic of D\u00fcsseldorf, Institute for Transplantation Diagnostics and Cell Therapeutics , D\u00fcsseldorf,","place":["Germany"]}]},{"given":"Fernando A","family":"Arosa","sequence":"additional","affiliation":[{"name":"Instituto de Biologia Molecular e Celular , Porto,","place":["Portugal"]},{"name":"Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar , Porto,","place":["Portugal"]},{"name":"Centro de Investiga\u00e7\u00e3o em Ci\u00eancias da Sa\u00fade, Instituto Superior de Ci\u00eancias da Sa\u00fade-Norte (ISCSN), Cooperativa de Ensino Superior Polit\u00e9cnico Universit\u00e1rio (CESPU) ,","place":["Portugal"]}]}],"member":"286","published-online":{"date-parts":[[2009,5,15]]},"reference":[{"key":"2026012806312254100_R1","first-page":"84","article-title":"Role of primary intrahepatic T-cell activation in the \u2018liver tolerance effect.\u2019.","volume-title":"Immunol. 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