Overexpression of the Runx3 Transcription Factor Increases the Proportion of Mature Thymocytes of the CD8 Single-Positive Lineage
The Runx family of transcription factors is thought to regulate the differentiation of thymocytes. Runx3 protein is detected mainly in the CD4(-)8(+) subset of T lymphocytes. In the thymus of Runx3-deficient mice, CD4 expression is de-repressed and CD4(-)8(+) thymocytes do not develop. This clearly...
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| Veröffentlicht in: | The Journal of immunology (1950) 2005-03, Vol.174 (5), p.2627-2636 |
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| creator | Kohu, Kazuyoshi Sato, Takehito Ohno, Shin-ichiro Hayashi, Keitaro Uchino, Ryuji Abe, Natsumi Nakazato, Megumi Yoshida, Naomi Kikuchi, Toshiaki Iwakura, Yoichiro Inoue, Yoshihiro Watanabe, Toshio Habu, Sonoko Satake, Masanobu |
| description | The Runx family of transcription factors is thought to regulate the differentiation of thymocytes. Runx3 protein is detected mainly in the CD4(-)8(+) subset of T lymphocytes. In the thymus of Runx3-deficient mice, CD4 expression is de-repressed and CD4(-)8(+) thymocytes do not develop. This clearly implicates Runx3 in CD4 silencing, but does not necessarily prove its role in the differentiation of CD4(-)8(+) thymocytes per se. In the present study, we created transgenic mice that overexpress Runx3 and analyzed the development of thymocytes in these animals. In the Runx3-transgenic thymus, the number of CD4(-)8(+) cells was greatly increased, whereas the numbers of CD4(+)8(+) and CD4(+)8(-) cells were reduced. The CD4(-)8(+) transgenic thymocytes contained mature cells with a TCR(high)HSA(low) phenotype. These cells were released from the thymus and contributed to the elevated level of CD4(-)8(+) cells relative to CD4(+)8(-) cells in the spleen. Runx3 overexpression also increased the number of mature CD4(-)8(+) thymocytes in mice with class II-restricted, transgenic TCR and in mice with a class I-deficient background, both of which are favorable for CD4(+)8(-) lineage selection. Thus, Runx3 can drive thymocytes to select the CD4(-)8(+) lineage. This activity is likely to be due to more than a simple silencing of CD4 gene expression. |
| doi_str_mv | 10.4049/jimmunol.174.5.2627 |
| format | Article |
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Runx3 protein is detected mainly in the CD4(-)8(+) subset of T lymphocytes. In the thymus of Runx3-deficient mice, CD4 expression is de-repressed and CD4(-)8(+) thymocytes do not develop. This clearly implicates Runx3 in CD4 silencing, but does not necessarily prove its role in the differentiation of CD4(-)8(+) thymocytes per se. In the present study, we created transgenic mice that overexpress Runx3 and analyzed the development of thymocytes in these animals. In the Runx3-transgenic thymus, the number of CD4(-)8(+) cells was greatly increased, whereas the numbers of CD4(+)8(+) and CD4(+)8(-) cells were reduced. The CD4(-)8(+) transgenic thymocytes contained mature cells with a TCR(high)HSA(low) phenotype. These cells were released from the thymus and contributed to the elevated level of CD4(-)8(+) cells relative to CD4(+)8(-) cells in the spleen. Runx3 overexpression also increased the number of mature CD4(-)8(+) thymocytes in mice with class II-restricted, transgenic TCR and in mice with a class I-deficient background, both of which are favorable for CD4(+)8(-) lineage selection. Thus, Runx3 can drive thymocytes to select the CD4(-)8(+) lineage. This activity is likely to be due to more than a simple silencing of CD4 gene expression.</description><identifier>ISSN: 0022-1767</identifier><identifier>EISSN: 1550-6606</identifier><identifier>DOI: 10.4049/jimmunol.174.5.2627</identifier><identifier>PMID: 15728469</identifier><language>eng</language><publisher>United States: Am Assoc Immnol</publisher><subject>Animals ; CD4 Antigens - biosynthesis ; CD4 Antigens - physiology ; CD4-Positive T-Lymphocytes - cytology ; CD4-Positive T-Lymphocytes - immunology ; CD4-Positive T-Lymphocytes - metabolism ; CD8 Antigens - biosynthesis ; CD8 Antigens - physiology ; CD8-Positive T-Lymphocytes - cytology ; CD8-Positive T-Lymphocytes - immunology ; CD8-Positive T-Lymphocytes - metabolism ; Cell Differentiation - genetics ; Cell Differentiation - immunology ; Cell Lineage - genetics ; Cell Lineage - immunology ; Cell Proliferation ; Core Binding Factor Alpha 3 Subunit ; DNA-Binding Proteins - biosynthesis ; DNA-Binding Proteins - genetics ; DNA-Binding Proteins - physiology ; Gene Expression Profiling ; Lymphocyte Count ; Mice ; Mice, Inbred C3H ; Mice, Inbred C57BL ; Mice, Transgenic ; Signal Transduction - genetics ; Signal Transduction - immunology ; T-Lymphocyte Subsets - cytology ; T-Lymphocyte Subsets - immunology ; T-Lymphocyte Subsets - metabolism ; Thymus Gland - cytology ; Thymus Gland - immunology ; Thymus Gland - metabolism ; Transcription Factors - biosynthesis ; Transcription Factors - genetics ; Transcription Factors - physiology</subject><ispartof>The Journal of immunology (1950), 2005-03, Vol.174 (5), p.2627-2636</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c477t-e9b4f664e7d94853058df8a0860de64d354f755fc12b8d02ff3ebd5bd571ed803</citedby><cites>FETCH-LOGICAL-c477t-e9b4f664e7d94853058df8a0860de64d354f755fc12b8d02ff3ebd5bd571ed803</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15728469$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kohu, Kazuyoshi</creatorcontrib><creatorcontrib>Sato, Takehito</creatorcontrib><creatorcontrib>Ohno, Shin-ichiro</creatorcontrib><creatorcontrib>Hayashi, Keitaro</creatorcontrib><creatorcontrib>Uchino, Ryuji</creatorcontrib><creatorcontrib>Abe, Natsumi</creatorcontrib><creatorcontrib>Nakazato, Megumi</creatorcontrib><creatorcontrib>Yoshida, Naomi</creatorcontrib><creatorcontrib>Kikuchi, Toshiaki</creatorcontrib><creatorcontrib>Iwakura, Yoichiro</creatorcontrib><creatorcontrib>Inoue, Yoshihiro</creatorcontrib><creatorcontrib>Watanabe, Toshio</creatorcontrib><creatorcontrib>Habu, Sonoko</creatorcontrib><creatorcontrib>Satake, Masanobu</creatorcontrib><title>Overexpression of the Runx3 Transcription Factor Increases the Proportion of Mature Thymocytes of the CD8 Single-Positive Lineage</title><title>The Journal of immunology (1950)</title><addtitle>J Immunol</addtitle><description>The Runx family of transcription factors is thought to regulate the differentiation of thymocytes. Runx3 protein is detected mainly in the CD4(-)8(+) subset of T lymphocytes. In the thymus of Runx3-deficient mice, CD4 expression is de-repressed and CD4(-)8(+) thymocytes do not develop. This clearly implicates Runx3 in CD4 silencing, but does not necessarily prove its role in the differentiation of CD4(-)8(+) thymocytes per se. In the present study, we created transgenic mice that overexpress Runx3 and analyzed the development of thymocytes in these animals. In the Runx3-transgenic thymus, the number of CD4(-)8(+) cells was greatly increased, whereas the numbers of CD4(+)8(+) and CD4(+)8(-) cells were reduced. The CD4(-)8(+) transgenic thymocytes contained mature cells with a TCR(high)HSA(low) phenotype. These cells were released from the thymus and contributed to the elevated level of CD4(-)8(+) cells relative to CD4(+)8(-) cells in the spleen. Runx3 overexpression also increased the number of mature CD4(-)8(+) thymocytes in mice with class II-restricted, transgenic TCR and in mice with a class I-deficient background, both of which are favorable for CD4(+)8(-) lineage selection. Thus, Runx3 can drive thymocytes to select the CD4(-)8(+) lineage. This activity is likely to be due to more than a simple silencing of CD4 gene expression.</description><subject>Animals</subject><subject>CD4 Antigens - biosynthesis</subject><subject>CD4 Antigens - physiology</subject><subject>CD4-Positive T-Lymphocytes - cytology</subject><subject>CD4-Positive T-Lymphocytes - immunology</subject><subject>CD4-Positive T-Lymphocytes - metabolism</subject><subject>CD8 Antigens - biosynthesis</subject><subject>CD8 Antigens - physiology</subject><subject>CD8-Positive T-Lymphocytes - cytology</subject><subject>CD8-Positive T-Lymphocytes - immunology</subject><subject>CD8-Positive T-Lymphocytes - metabolism</subject><subject>Cell Differentiation - genetics</subject><subject>Cell Differentiation - immunology</subject><subject>Cell Lineage - genetics</subject><subject>Cell Lineage - immunology</subject><subject>Cell Proliferation</subject><subject>Core Binding Factor Alpha 3 Subunit</subject><subject>DNA-Binding Proteins - biosynthesis</subject><subject>DNA-Binding Proteins - genetics</subject><subject>DNA-Binding Proteins - physiology</subject><subject>Gene Expression Profiling</subject><subject>Lymphocyte Count</subject><subject>Mice</subject><subject>Mice, Inbred C3H</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Transgenic</subject><subject>Signal Transduction - genetics</subject><subject>Signal Transduction - immunology</subject><subject>T-Lymphocyte Subsets - cytology</subject><subject>T-Lymphocyte Subsets - immunology</subject><subject>T-Lymphocyte Subsets - metabolism</subject><subject>Thymus Gland - cytology</subject><subject>Thymus Gland - immunology</subject><subject>Thymus Gland - metabolism</subject><subject>Transcription Factors - biosynthesis</subject><subject>Transcription Factors - genetics</subject><subject>Transcription Factors - physiology</subject><issn>0022-1767</issn><issn>1550-6606</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkctu2zAQRYmiQeIm-YIChVbtSg4p8eVl4TRpAAcOWmdN0NLQpiGJKkn5scyfV65VJLsAA8xizr2LOQh9JnhMMZ3cbGxdd42rxkTQMRtnPBMf0IgwhlPOMf-IRhhnWUoEFxfoUwgbjDHHGT1HF4SJTFI-GaGX-RY87FsPIVjXJM4kcQ3Jr67Z58nC6yYU3rbxeLrTRXQ-eWgKDzpA-Ac-edc6H4foo46dh2SxPtSuOMSeGfqmtzL5bZtVBemTCzbaLSQz24BewRU6M7oKcD3sS_R892Mx_ZnO5vcP0--ztKBCxBQmS2o4pyDKCZUsx0yWRmosOS6B0zJn1AjGTEGypSxxZkwOy5L1IwiUEueX6Oupt_XuTwchqtqGAqpKN-C6oLigTHBJ3gWJEDzvH9yD-QksvAvBg1Gtt7X2B0WwOipS_xX1GaqYOirqU1-G-m5ZQ_maGZz0wLcTsLar9c56UKHWVdXjRO12uzdVfwEEWZ7b</recordid><startdate>20050301</startdate><enddate>20050301</enddate><creator>Kohu, Kazuyoshi</creator><creator>Sato, Takehito</creator><creator>Ohno, Shin-ichiro</creator><creator>Hayashi, Keitaro</creator><creator>Uchino, Ryuji</creator><creator>Abe, Natsumi</creator><creator>Nakazato, Megumi</creator><creator>Yoshida, Naomi</creator><creator>Kikuchi, Toshiaki</creator><creator>Iwakura, Yoichiro</creator><creator>Inoue, Yoshihiro</creator><creator>Watanabe, Toshio</creator><creator>Habu, Sonoko</creator><creator>Satake, Masanobu</creator><general>Am Assoc Immnol</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></search><sort><creationdate>20050301</creationdate><title>Overexpression of the Runx3 Transcription Factor Increases the Proportion of Mature Thymocytes of the CD8 Single-Positive Lineage</title><author>Kohu, Kazuyoshi ; Sato, Takehito ; Ohno, Shin-ichiro ; Hayashi, Keitaro ; Uchino, Ryuji ; Abe, Natsumi ; Nakazato, Megumi ; Yoshida, Naomi ; Kikuchi, Toshiaki ; Iwakura, Yoichiro ; Inoue, Yoshihiro ; Watanabe, Toshio ; Habu, Sonoko ; Satake, Masanobu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c477t-e9b4f664e7d94853058df8a0860de64d354f755fc12b8d02ff3ebd5bd571ed803</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Animals</topic><topic>CD4 Antigens - biosynthesis</topic><topic>CD4 Antigens - physiology</topic><topic>CD4-Positive T-Lymphocytes - cytology</topic><topic>CD4-Positive T-Lymphocytes - immunology</topic><topic>CD4-Positive T-Lymphocytes - metabolism</topic><topic>CD8 Antigens - biosynthesis</topic><topic>CD8 Antigens - physiology</topic><topic>CD8-Positive T-Lymphocytes - cytology</topic><topic>CD8-Positive T-Lymphocytes - immunology</topic><topic>CD8-Positive T-Lymphocytes - metabolism</topic><topic>Cell Differentiation - genetics</topic><topic>Cell Differentiation - immunology</topic><topic>Cell Lineage - genetics</topic><topic>Cell Lineage - immunology</topic><topic>Cell Proliferation</topic><topic>Core Binding Factor Alpha 3 Subunit</topic><topic>DNA-Binding Proteins - biosynthesis</topic><topic>DNA-Binding Proteins - genetics</topic><topic>DNA-Binding Proteins - physiology</topic><topic>Gene Expression Profiling</topic><topic>Lymphocyte Count</topic><topic>Mice</topic><topic>Mice, Inbred C3H</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Transgenic</topic><topic>Signal Transduction - genetics</topic><topic>Signal Transduction - immunology</topic><topic>T-Lymphocyte Subsets - cytology</topic><topic>T-Lymphocyte Subsets - immunology</topic><topic>T-Lymphocyte Subsets - metabolism</topic><topic>Thymus Gland - cytology</topic><topic>Thymus Gland - immunology</topic><topic>Thymus Gland - metabolism</topic><topic>Transcription Factors - biosynthesis</topic><topic>Transcription Factors - genetics</topic><topic>Transcription Factors - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kohu, Kazuyoshi</creatorcontrib><creatorcontrib>Sato, Takehito</creatorcontrib><creatorcontrib>Ohno, Shin-ichiro</creatorcontrib><creatorcontrib>Hayashi, Keitaro</creatorcontrib><creatorcontrib>Uchino, Ryuji</creatorcontrib><creatorcontrib>Abe, Natsumi</creatorcontrib><creatorcontrib>Nakazato, Megumi</creatorcontrib><creatorcontrib>Yoshida, Naomi</creatorcontrib><creatorcontrib>Kikuchi, Toshiaki</creatorcontrib><creatorcontrib>Iwakura, Yoichiro</creatorcontrib><creatorcontrib>Inoue, Yoshihiro</creatorcontrib><creatorcontrib>Watanabe, Toshio</creatorcontrib><creatorcontrib>Habu, Sonoko</creatorcontrib><creatorcontrib>Satake, Masanobu</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><jtitle>The Journal of immunology (1950)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kohu, Kazuyoshi</au><au>Sato, Takehito</au><au>Ohno, Shin-ichiro</au><au>Hayashi, Keitaro</au><au>Uchino, Ryuji</au><au>Abe, Natsumi</au><au>Nakazato, Megumi</au><au>Yoshida, Naomi</au><au>Kikuchi, Toshiaki</au><au>Iwakura, Yoichiro</au><au>Inoue, Yoshihiro</au><au>Watanabe, Toshio</au><au>Habu, Sonoko</au><au>Satake, Masanobu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Overexpression of the Runx3 Transcription Factor Increases the Proportion of Mature Thymocytes of the CD8 Single-Positive Lineage</atitle><jtitle>The Journal of immunology (1950)</jtitle><addtitle>J Immunol</addtitle><date>2005-03-01</date><risdate>2005</risdate><volume>174</volume><issue>5</issue><spage>2627</spage><epage>2636</epage><pages>2627-2636</pages><issn>0022-1767</issn><eissn>1550-6606</eissn><abstract>The Runx family of transcription factors is thought to regulate the differentiation of thymocytes. Runx3 protein is detected mainly in the CD4(-)8(+) subset of T lymphocytes. In the thymus of Runx3-deficient mice, CD4 expression is de-repressed and CD4(-)8(+) thymocytes do not develop. This clearly implicates Runx3 in CD4 silencing, but does not necessarily prove its role in the differentiation of CD4(-)8(+) thymocytes per se. In the present study, we created transgenic mice that overexpress Runx3 and analyzed the development of thymocytes in these animals. In the Runx3-transgenic thymus, the number of CD4(-)8(+) cells was greatly increased, whereas the numbers of CD4(+)8(+) and CD4(+)8(-) cells were reduced. The CD4(-)8(+) transgenic thymocytes contained mature cells with a TCR(high)HSA(low) phenotype. These cells were released from the thymus and contributed to the elevated level of CD4(-)8(+) cells relative to CD4(+)8(-) cells in the spleen. Runx3 overexpression also increased the number of mature CD4(-)8(+) thymocytes in mice with class II-restricted, transgenic TCR and in mice with a class I-deficient background, both of which are favorable for CD4(+)8(-) lineage selection. Thus, Runx3 can drive thymocytes to select the CD4(-)8(+) lineage. This activity is likely to be due to more than a simple silencing of CD4 gene expression.</abstract><cop>United States</cop><pub>Am Assoc Immnol</pub><pmid>15728469</pmid><doi>10.4049/jimmunol.174.5.2627</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals CD4 Antigens - biosynthesis CD4 Antigens - physiology CD4-Positive T-Lymphocytes - cytology CD4-Positive T-Lymphocytes - immunology CD4-Positive T-Lymphocytes - metabolism CD8 Antigens - biosynthesis CD8 Antigens - physiology CD8-Positive T-Lymphocytes - cytology CD8-Positive T-Lymphocytes - immunology CD8-Positive T-Lymphocytes - metabolism Cell Differentiation - genetics Cell Differentiation - immunology Cell Lineage - genetics Cell Lineage - immunology Cell Proliferation Core Binding Factor Alpha 3 Subunit DNA-Binding Proteins - biosynthesis DNA-Binding Proteins - genetics DNA-Binding Proteins - physiology Gene Expression Profiling Lymphocyte Count Mice Mice, Inbred C3H Mice, Inbred C57BL Mice, Transgenic Signal Transduction - genetics Signal Transduction - immunology T-Lymphocyte Subsets - cytology T-Lymphocyte Subsets - immunology T-Lymphocyte Subsets - metabolism Thymus Gland - cytology Thymus Gland - immunology Thymus Gland - metabolism Transcription Factors - biosynthesis Transcription Factors - genetics Transcription Factors - physiology |
| title | Overexpression of the Runx3 Transcription Factor Increases the Proportion of Mature Thymocytes of the CD8 Single-Positive Lineage |
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