Comparison of intrahepatic lymphocytes from normal and growth hormone transgenic mice with chronic hepatitis and liver cancer
SUMMARY Mice expressing an ovine growth hormone–mouse metallothionein promoter fusion gene (METoGH mice) develop chronic hepatitis which becomes progressively more severe over time, hepatocellular adenomas, and eventually carcinoma in the oldest animals. T‐lymphocyte expression of activation/memory‐...
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Veröffentlicht in: | Immunology 1997-03, Vol.90 (3), p.412-420 |
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description | SUMMARY
Mice expressing an ovine growth hormone–mouse metallothionein promoter fusion gene (METoGH mice) develop chronic hepatitis which becomes progressively more severe over time, hepatocellular adenomas, and eventually carcinoma in the oldest animals. T‐lymphocyte expression of activation/memory‐associated markers was compared between liver and blood lymphocytes isolated from METoGH and non‐transgenic mice at 7, 10 and 12 months of age. The percentage of intrahepatic lymphocytes (IHL) which were CD4+ was markedly diminished in METoGH mice at all times. CD4+ and CD8+ IHL in METoGH mice expressed Ly‐6A/6D at increased density, and were CD45RBlo at later time‐points. Ly‐6C+ and NK1.1+ CD4+ cells, which are common in normal mouse liver, were found at decreased frequency in METoGH livers. Further analysis demonstrated that, as a proportion of total T‐cell receptor (TCR)αβ cells, NK1.1+ TCRαβint CD4+ cell numbers (NKT cells) were diminished in the livers of METoGH mice. Observations made in METoGH mice support the hypothesis that sustained liver inflammation and hepatocellular injury may be linked to liver cancer. Additionally, it is possible that the relative lack of NKT cells may create an environment permissive for the growth of liver tumours. |
doi_str_mv | 10.1111/j.1365-2567.1997.00412.x |
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Mice expressing an ovine growth hormone–mouse metallothionein promoter fusion gene (METoGH mice) develop chronic hepatitis which becomes progressively more severe over time, hepatocellular adenomas, and eventually carcinoma in the oldest animals. T‐lymphocyte expression of activation/memory‐associated markers was compared between liver and blood lymphocytes isolated from METoGH and non‐transgenic mice at 7, 10 and 12 months of age. The percentage of intrahepatic lymphocytes (IHL) which were CD4+ was markedly diminished in METoGH mice at all times. CD4+ and CD8+ IHL in METoGH mice expressed Ly‐6A/6D at increased density, and were CD45RBlo at later time‐points. Ly‐6C+ and NK1.1+ CD4+ cells, which are common in normal mouse liver, were found at decreased frequency in METoGH livers. Further analysis demonstrated that, as a proportion of total T‐cell receptor (TCR)αβ cells, NK1.1+ TCRαβint CD4+ cell numbers (NKT cells) were diminished in the livers of METoGH mice. Observations made in METoGH mice support the hypothesis that sustained liver inflammation and hepatocellular injury may be linked to liver cancer. Additionally, it is possible that the relative lack of NKT cells may create an environment permissive for the growth of liver tumours.</description><identifier>ISSN: 0019-2805</identifier><identifier>EISSN: 1365-2567</identifier><identifier>DOI: 10.1111/j.1365-2567.1997.00412.x</identifier><identifier>PMID: 9155649</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Animals ; CD4-Positive T-Lymphocytes - immunology ; Cell Transformation, Neoplastic - immunology ; Chronic Disease ; Disease Progression ; Growth Hormone - genetics ; Hepatitis - immunology ; Immunophenotyping ; Liver - immunology ; Liver - pathology ; Liver Neoplasms - immunology ; Mice ; Mice, Transgenic ; T-Lymphocyte Subsets - immunology</subject><ispartof>Immunology, 1997-03, Vol.90 (3), p.412-420</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4992-fe1462f3bdc6c507e1bde8da5c2ec3f0b690ba4bafc14f6b79719fcaaae666803</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1456602/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1456602/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,1411,1427,27901,27902,45550,45551,46384,46808,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9155649$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>HARDY, C. L.</creatorcontrib><creatorcontrib>BHATHAL, P. S.</creatorcontrib><creatorcontrib>SNIBSON, K. J.</creatorcontrib><creatorcontrib>ADAMS, T. E.</creatorcontrib><title>Comparison of intrahepatic lymphocytes from normal and growth hormone transgenic mice with chronic hepatitis and liver cancer</title><title>Immunology</title><addtitle>Immunology</addtitle><description>SUMMARY
Mice expressing an ovine growth hormone–mouse metallothionein promoter fusion gene (METoGH mice) develop chronic hepatitis which becomes progressively more severe over time, hepatocellular adenomas, and eventually carcinoma in the oldest animals. T‐lymphocyte expression of activation/memory‐associated markers was compared between liver and blood lymphocytes isolated from METoGH and non‐transgenic mice at 7, 10 and 12 months of age. The percentage of intrahepatic lymphocytes (IHL) which were CD4+ was markedly diminished in METoGH mice at all times. CD4+ and CD8+ IHL in METoGH mice expressed Ly‐6A/6D at increased density, and were CD45RBlo at later time‐points. Ly‐6C+ and NK1.1+ CD4+ cells, which are common in normal mouse liver, were found at decreased frequency in METoGH livers. Further analysis demonstrated that, as a proportion of total T‐cell receptor (TCR)αβ cells, NK1.1+ TCRαβint CD4+ cell numbers (NKT cells) were diminished in the livers of METoGH mice. Observations made in METoGH mice support the hypothesis that sustained liver inflammation and hepatocellular injury may be linked to liver cancer. Additionally, it is possible that the relative lack of NKT cells may create an environment permissive for the growth of liver tumours.</description><subject>Animals</subject><subject>CD4-Positive T-Lymphocytes - immunology</subject><subject>Cell Transformation, Neoplastic - immunology</subject><subject>Chronic Disease</subject><subject>Disease Progression</subject><subject>Growth Hormone - genetics</subject><subject>Hepatitis - immunology</subject><subject>Immunophenotyping</subject><subject>Liver - immunology</subject><subject>Liver - pathology</subject><subject>Liver Neoplasms - immunology</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>T-Lymphocyte Subsets - immunology</subject><issn>0019-2805</issn><issn>1365-2567</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1997</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkUFv1DAQhS1EVZbCT0DyiVuCncROLCEktCpQqVUv7dlynPHGq8QOdrbbPfDfcbqrFZzAF3vmzXvy6EMIU5LTdD5tc1pylhWM1zkVos4JqWiRP79Cq7PwGq0IoSIrGsLeoLcxblNZEsYu0aWgjPFKrNCvtR8nFWz0DnuDrZuD6mFSs9V4OIxT7_VhhohN8CN2PoxqwMp1eBP8fu5xnzreAU4uFzfgkmu0GvDeJlH3wS-dY95s44tzsE8QsFZOQ3iHLowaIrw_3Vfo8dv1w_pHdnv__Wb99TbTlRBFZoBWvDBl22muGamBth00nWK6AF0a0nJBWlW1ymhaGd7WoqbCaKUUcM4bUl6hL8fcadeO0GlY1hzkFOyowkF6ZeXfirO93PgnSSvGOSlSwMdTQPA_dxBnOdqoYRiUA7-LshaEMsrIPwcpJ2XdCJYGm-OgDj7GAOb8G0rkwlhu5YJSLijlwli-MJbPyfrhz23OxhPUpH8-6ns7wOG_c-XN3V16lL8B-GS6tw</recordid><startdate>199703</startdate><enddate>199703</enddate><creator>HARDY, C. L.</creator><creator>BHATHAL, P. S.</creator><creator>SNIBSON, K. J.</creator><creator>ADAMS, T. E.</creator><general>Blackwell Publishing Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>H94</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>199703</creationdate><title>Comparison of intrahepatic lymphocytes from normal and growth hormone transgenic mice with chronic hepatitis and liver cancer</title><author>HARDY, C. L. ; BHATHAL, P. S. ; SNIBSON, K. J. ; ADAMS, T. E.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4992-fe1462f3bdc6c507e1bde8da5c2ec3f0b690ba4bafc14f6b79719fcaaae666803</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1997</creationdate><topic>Animals</topic><topic>CD4-Positive T-Lymphocytes - immunology</topic><topic>Cell Transformation, Neoplastic - immunology</topic><topic>Chronic Disease</topic><topic>Disease Progression</topic><topic>Growth Hormone - genetics</topic><topic>Hepatitis - immunology</topic><topic>Immunophenotyping</topic><topic>Liver - immunology</topic><topic>Liver - pathology</topic><topic>Liver Neoplasms - immunology</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>T-Lymphocyte Subsets - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>HARDY, C. L.</creatorcontrib><creatorcontrib>BHATHAL, P. S.</creatorcontrib><creatorcontrib>SNIBSON, K. J.</creatorcontrib><creatorcontrib>ADAMS, T. E.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>HARDY, C. L.</au><au>BHATHAL, P. S.</au><au>SNIBSON, K. J.</au><au>ADAMS, T. E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Comparison of intrahepatic lymphocytes from normal and growth hormone transgenic mice with chronic hepatitis and liver cancer</atitle><jtitle>Immunology</jtitle><addtitle>Immunology</addtitle><date>1997-03</date><risdate>1997</risdate><volume>90</volume><issue>3</issue><spage>412</spage><epage>420</epage><pages>412-420</pages><issn>0019-2805</issn><eissn>1365-2567</eissn><abstract>SUMMARY
Mice expressing an ovine growth hormone–mouse metallothionein promoter fusion gene (METoGH mice) develop chronic hepatitis which becomes progressively more severe over time, hepatocellular adenomas, and eventually carcinoma in the oldest animals. T‐lymphocyte expression of activation/memory‐associated markers was compared between liver and blood lymphocytes isolated from METoGH and non‐transgenic mice at 7, 10 and 12 months of age. The percentage of intrahepatic lymphocytes (IHL) which were CD4+ was markedly diminished in METoGH mice at all times. CD4+ and CD8+ IHL in METoGH mice expressed Ly‐6A/6D at increased density, and were CD45RBlo at later time‐points. Ly‐6C+ and NK1.1+ CD4+ cells, which are common in normal mouse liver, were found at decreased frequency in METoGH livers. Further analysis demonstrated that, as a proportion of total T‐cell receptor (TCR)αβ cells, NK1.1+ TCRαβint CD4+ cell numbers (NKT cells) were diminished in the livers of METoGH mice. Observations made in METoGH mice support the hypothesis that sustained liver inflammation and hepatocellular injury may be linked to liver cancer. Additionally, it is possible that the relative lack of NKT cells may create an environment permissive for the growth of liver tumours.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>9155649</pmid><doi>10.1111/j.1365-2567.1997.00412.x</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Animals CD4-Positive T-Lymphocytes - immunology Cell Transformation, Neoplastic - immunology Chronic Disease Disease Progression Growth Hormone - genetics Hepatitis - immunology Immunophenotyping Liver - immunology Liver - pathology Liver Neoplasms - immunology Mice Mice, Transgenic T-Lymphocyte Subsets - immunology |
title | Comparison of intrahepatic lymphocytes from normal and growth hormone transgenic mice with chronic hepatitis and liver cancer |
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