{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T19:34:33Z","timestamp":1791056073603,"version":"4.1.0"},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2007,3,7]],"date-time":"2007-03-07T00:00:00Z","timestamp":1173225600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2007,3,9]]},"abstract":"<jats:title>Summary<\/jats:title>\n               <jats:p>Recent functional research studies suggest an anti-fibrotic role for natural killer (NK) cells coupled with a profibrotic role for CD8 cells. However, the morphological cellular interplay between the different cell types is less clear. To investigate lymphocyte\/hepatic stellate cell (HSC) interactions, hepatic fibrosis was induced by administering carbon tetrachloride (CCl4) intraperitoneally (i.p.) for 4 weeks in C57Bl\/6 mice. Animals were killed at 0, 1, 2, 3 and 4 weeks. Liver sections were stained for Sirius red. Confocal microscopy was used to evaluate alpha smooth-muscle actin (\u03b1SMA) and lymphocyte subsets in liver sections. At weeks 0 and 4, liver protein extracts were assessed for \u03b1SMA by Western blotting and isolated liver lymphocytes as well as HSC were analysed by fluorescence activated cell sorter (FACS). Similar to the results obtained from classical Sirius red staining and \u03b1SMA blotting, analysis of liver sections by confocal microscopy revealed a marked and continuous accumulation of \u03b1SMA staining along sequential experimental check-points after administering CCl4. Although the number of all liver lymphocyte subsets increased following fibrosis induction, FACS analysis revealed an increase in the distribution of liver CD8 subsets and a decrease of CD4 T cells. Confocal microscopy showed a significant early appearance of CD8 and NK cells, and to a lesser extent CD4 T cells, appearing only from week 2. Lymphocytes were seen in proximity only to HSC, mainly in the periportal area and along fibrotic septa, suggesting a direct interaction. Notably, lymphocyte subsets were undetectable in naive liver sections. Freshly isolated HCS show high expression of major histocompatibility complex (MHC) class II and CD11c. In the animal model of hepatic fibrosis, lymphocytes infiltrate into the liver parenchyma and it is thought that they attach directly to activated HSC. Because HSCs express CD11c\/class II molecules, interactions involving them might reflect that HSCs have an antigen-presenting capacity.<\/jats:p>","DOI":"10.1111\/j.1365-2249.2007.03353.x","type":"journal-article","created":{"date-parts":[[2008,10,15]],"date-time":"2008-10-15T12:36:33Z","timestamp":1224074193000},"page":"338-347","source":"Crossref","is-referenced-by-count":65,"title":["Lymphocyte\u2013hepatic stellate cell proximity suggests a direct interaction"],"prefix":"10.1093","volume":"148","author":[{"given":"N","family":"Muhanna","sequence":"first","affiliation":[{"name":"Liver\/Gastroenterology Units, Division of Medicine, Hadassah University Hospital, Jerusalem, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Horani","sequence":"additional","affiliation":[{"name":"Liver\/Gastroenterology Units, Division of Medicine, Hadassah University Hospital, Jerusalem, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Doron","sequence":"additional","affiliation":[{"name":"Liver\/Gastroenterology Units, Division of Medicine, Hadassah University Hospital, Jerusalem, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"Safadi","sequence":"additional","affiliation":[{"name":"Liver\/Gastroenterology Units, Division of Medicine, Hadassah University Hospital, Jerusalem, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2007,3,7]]},"reference":[{"key":"2022010414521141500_b1","doi-asserted-by":"crossref","first-page":"2247","DOI":"10.1074\/jbc.275.4.2247","article-title":"Molecular regulation of hepatic fibrosis, an integrated cellular response to tissue injury","volume":"275","author":"Friedman","year":"2000","journal-title":"J Biol Chem"},{"key":"2022010414521141500_b2","doi-asserted-by":"crossref","first-page":"S38","DOI":"10.1016\/S0168-8278(02)00429-4","article-title":"Liver fibrosis\u2003\u2212\u2003from bench to bedside","volume":"38","author":"Friedman","year":"2003","journal-title":"J Hepatol"},{"key":"2022010414521141500_b3","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1053\/j.gastro.2004.02.025","article-title":"A significant proportion of myofibroblasts are of bone marrow origin in human liver fibrosis","volume":"126","author":"Forbes","year":"2004","journal-title":"Gastroenterology"},{"key":"2022010414521141500_b4","doi-asserted-by":"crossref","first-page":"d793","DOI":"10.2741\/gressner","article-title":"Roles of TGF-beta in hepatic fibrosis","volume":"7","author":"Gressner","year":"2002","journal-title":"Front Biosci"},{"key":"2022010414521141500_b5","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1074\/jbc.273.1.302","article-title":"Expression of interleukin-10 by in vitro and in vivo activated hepatic stellate cells","volume":"273","author":"Wang","year":"1998","journal-title":"J Biol Chem"},{"key":"2022010414521141500_b6","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.1002\/hep.510280620","article-title":"Interleukin-10 expression and function in experimental murine liver inflammation and fibrosis","volume":"28","author":"Thompson","year":"1998","journal-title":"Hepatology"},{"key":"2022010414521141500_b7","doi-asserted-by":"crossref","first-page":"10663","DOI":"10.1073\/pnas.94.20.10663","article-title":"Strain-specific differences in mouse hepatic wound healing are mediated by divergent T helper cytokine responses","volume":"94","author":"Shi","year":"1997","journal-title":"Proc Natl Acad Sci USA"},{"key":"2022010414521141500_b8","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1084\/jem.179.4.1367","article-title":"CD4+ effector cells default to the Th2 pathway in interferon gamma-deficient mice infected with Leishmania major","volume":"179","author":"Wang","year":"1994","journal-title":"J Exp Med"},{"key":"2022010414521141500_b9","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1126\/science.271.5251.984","article-title":"Genetic susceptibility to Leishmania: IL-12 responsiveness in TH1 cell development","volume":"271","author":"Guler","year":"1996","journal-title":"Science"},{"key":"2022010414521141500_b10","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1084\/jem.169.1.59","article-title":"Reciprocal expression of interferon gamma or interleukin 4 during the resolution or progression of murine leishmaniasis. 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