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Altered Development of CD8 + T Cell Lineages in Mice Deficient for the Tec Kinases Itk and Rlk
Mutations affecting the Tec kinases Itk and Rlk decrease T cell receptor-induced Ca 2+ mobilization and Erk kinase activation and impair both positive and negative thymic selection. Itk −/− and Rlk −/−Itk −/− mice also have decreased CD4:8 T cell ratios, suggestive of altered CD4:8 lineage commitmen...
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| Published in: | Immunity (Cambridge, Mass.) Mass.), 2006-07, Vol.25 (1), p.93-104 |
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| Main Authors: | , , , , , , , , |
| Format: | Article |
| Language: | English |
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| cited_by | cdi_FETCH-LOGICAL-c434t-188d3ab00fc0a60c61455efdf0161e64738e7207471d0d320f063b8922f4f88a3 |
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| cites | cdi_FETCH-LOGICAL-c434t-188d3ab00fc0a60c61455efdf0161e64738e7207471d0d320f063b8922f4f88a3 |
| container_end_page | 104 |
| container_issue | 1 |
| container_start_page | 93 |
| container_title | Immunity (Cambridge, Mass.) |
| container_volume | 25 |
| creator | Broussard, Christine Fleischecker, Christine Horai, Reiko Chetana, Madeva Venegas, Ana M. Sharp, Leslie L. Hedrick, Stephen M. Fowlkes, B.J. Schwartzberg, Pamela L. |
| description | Mutations affecting the Tec kinases Itk and Rlk decrease T cell receptor-induced Ca
2+ mobilization and Erk kinase activation and impair both positive and negative thymic selection.
Itk
−/−
and
Rlk
−/−Itk
−/−
mice also have decreased CD4:8 T cell ratios, suggestive of altered CD4:8 lineage commitment. Nonetheless, we find that CD8 single-positive (SP) thymocytes and peripheral CD8
+ T cells in these mice do not resemble conventional CD8
+ T cells. Instead, these cells express memory markers, rapidly produce interferon-γ, and can be selected on hematopoietically derived cells, similar to MHC class Ib-restricted “innate-type” lymphocytes. Itk deficiency also greatly increases the number of cells selected by MHC class Ib. Expression of a hypersensitive Erk2 mutant partially corrects the CD8
+ T cell phenotypes in
Itk
−/−
mice, arguing that altered signaling permits development of this innate-type CD8
+ cell population. Our results suggest that Tec kinases differentially regulate development of conventional versus nonconventional lymphocytes. |
| doi_str_mv | 10.1016/j.immuni.2006.05.011 |
| format | article |
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2+ mobilization and Erk kinase activation and impair both positive and negative thymic selection.
Itk
−/−
and
Rlk
−/−Itk
−/−
mice also have decreased CD4:8 T cell ratios, suggestive of altered CD4:8 lineage commitment. Nonetheless, we find that CD8 single-positive (SP) thymocytes and peripheral CD8
+ T cells in these mice do not resemble conventional CD8
+ T cells. Instead, these cells express memory markers, rapidly produce interferon-γ, and can be selected on hematopoietically derived cells, similar to MHC class Ib-restricted “innate-type” lymphocytes. Itk deficiency also greatly increases the number of cells selected by MHC class Ib. Expression of a hypersensitive Erk2 mutant partially corrects the CD8
+ T cell phenotypes in
Itk
−/−
mice, arguing that altered signaling permits development of this innate-type CD8
+ cell population. Our results suggest that Tec kinases differentially regulate development of conventional versus nonconventional lymphocytes.</description><identifier>ISSN: 1074-7613</identifier><identifier>EISSN: 1097-4180</identifier><identifier>DOI: 10.1016/j.immuni.2006.05.011</identifier><identifier>PMID: 16860760</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Bone marrow ; CD8-Positive T-Lymphocytes - cytology ; CD8-Positive T-Lymphocytes - enzymology ; CD8-Positive T-Lymphocytes - immunology ; Cell Differentiation ; Cell Lineage ; CELLIMMUNO ; DEVBIO ; Flow cytometry ; Histocompatibility Antigens - metabolism ; Immune system ; Kinases ; Lymphocytes ; Mice ; Mice, Knockout ; Organ Culture Techniques ; Peptides ; Phenotype ; Protein-Tyrosine Kinases - classification ; Protein-Tyrosine Kinases - deficiency ; Protein-Tyrosine Kinases - genetics ; Protein-Tyrosine Kinases - metabolism ; Signal Transduction ; SIGNALING ; T cell receptors ; Thymus Gland - cytology ; Thymus Gland - immunology ; Thymus Gland - metabolism ; Time Factors</subject><ispartof>Immunity (Cambridge, Mass.), 2006-07, Vol.25 (1), p.93-104</ispartof><rights>2006 Elsevier Inc.</rights><rights>Copyright Elsevier Limited Jul 2006</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c434t-188d3ab00fc0a60c61455efdf0161e64738e7207471d0d320f063b8922f4f88a3</citedby><cites>FETCH-LOGICAL-c434t-188d3ab00fc0a60c61455efdf0161e64738e7207471d0d320f063b8922f4f88a3</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/16860760$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Broussard, Christine</creatorcontrib><creatorcontrib>Fleischecker, Christine</creatorcontrib><creatorcontrib>Horai, Reiko</creatorcontrib><creatorcontrib>Chetana, Madeva</creatorcontrib><creatorcontrib>Venegas, Ana M.</creatorcontrib><creatorcontrib>Sharp, Leslie L.</creatorcontrib><creatorcontrib>Hedrick, Stephen M.</creatorcontrib><creatorcontrib>Fowlkes, B.J.</creatorcontrib><creatorcontrib>Schwartzberg, Pamela L.</creatorcontrib><title>Altered Development of CD8 + T Cell Lineages in Mice Deficient for the Tec Kinases Itk and Rlk</title><title>Immunity (Cambridge, Mass.)</title><addtitle>Immunity</addtitle><description>Mutations affecting the Tec kinases Itk and Rlk decrease T cell receptor-induced Ca
2+ mobilization and Erk kinase activation and impair both positive and negative thymic selection.
Itk
−/−
and
Rlk
−/−Itk
−/−
mice also have decreased CD4:8 T cell ratios, suggestive of altered CD4:8 lineage commitment. Nonetheless, we find that CD8 single-positive (SP) thymocytes and peripheral CD8
+ T cells in these mice do not resemble conventional CD8
+ T cells. Instead, these cells express memory markers, rapidly produce interferon-γ, and can be selected on hematopoietically derived cells, similar to MHC class Ib-restricted “innate-type” lymphocytes. Itk deficiency also greatly increases the number of cells selected by MHC class Ib. Expression of a hypersensitive Erk2 mutant partially corrects the CD8
+ T cell phenotypes in
Itk
−/−
mice, arguing that altered signaling permits development of this innate-type CD8
+ cell population. Our results suggest that Tec kinases differentially regulate development of conventional versus nonconventional lymphocytes.</description><subject>Animals</subject><subject>Bone marrow</subject><subject>CD8-Positive T-Lymphocytes - cytology</subject><subject>CD8-Positive T-Lymphocytes - enzymology</subject><subject>CD8-Positive T-Lymphocytes - immunology</subject><subject>Cell Differentiation</subject><subject>Cell Lineage</subject><subject>CELLIMMUNO</subject><subject>DEVBIO</subject><subject>Flow cytometry</subject><subject>Histocompatibility Antigens - metabolism</subject><subject>Immune system</subject><subject>Kinases</subject><subject>Lymphocytes</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Organ Culture Techniques</subject><subject>Peptides</subject><subject>Phenotype</subject><subject>Protein-Tyrosine Kinases - classification</subject><subject>Protein-Tyrosine Kinases - deficiency</subject><subject>Protein-Tyrosine Kinases - genetics</subject><subject>Protein-Tyrosine Kinases - metabolism</subject><subject>Signal Transduction</subject><subject>SIGNALING</subject><subject>T cell receptors</subject><subject>Thymus Gland - cytology</subject><subject>Thymus Gland - immunology</subject><subject>Thymus Gland - metabolism</subject><subject>Time Factors</subject><issn>1074-7613</issn><issn>1097-4180</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><recordid>eNp9kE1rGzEQhkVJqZM0_6AUQSCXsNvRrlYrXwrB-aQugeJeI2Rp1MreD0faDeTfV4sNhRxy0hyeGb3vQ8gXBjkDJr5tct-2Y-fzAkDkUOXA2AdyzGBeZ5xJOJrmmme1YOWMnMS4AWC8msMnMmNCCqgFHJOnq2bAgJZe4ws2_a7FbqC9o4trSS_pii6waejSd6j_YKS-oz-9wQQ7b_yEuj7Q4S_SFRr6w3c6Juph2FLdWfqr2X4mH51uIp4d3lPy-_ZmtbjPlo93D4urZWZ4yYeMSWlLvQZwBrQAI1LQCp11qShDwetSYl2kNjWzYMsCHIhyLedF4biTUpen5GJ_dxf65xHjoFofTcquO-zHqFJfIedcJvD8Dbjpx9ClbIpVwIuykqxKFN9TJvQxBnRqF3yrw6tioCb7aqP29tVkX0Glkv209vVwfFy3aP8vHXQn4PsewOTixWNQcdJo0PqAZlC29-__8A8SipPe</recordid><startdate>20060701</startdate><enddate>20060701</enddate><creator>Broussard, Christine</creator><creator>Fleischecker, Christine</creator><creator>Horai, Reiko</creator><creator>Chetana, Madeva</creator><creator>Venegas, Ana M.</creator><creator>Sharp, Leslie L.</creator><creator>Hedrick, Stephen M.</creator><creator>Fowlkes, B.J.</creator><creator>Schwartzberg, Pamela L.</creator><general>Elsevier Inc</general><general>Elsevier Limited</general><scope>6I.</scope><scope>AAFTH</scope><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>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7T7</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>NAPCQ</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20060701</creationdate><title>Altered Development of CD8 + T Cell Lineages in Mice Deficient for the Tec Kinases Itk and Rlk</title><author>Broussard, Christine ; Fleischecker, Christine ; Horai, Reiko ; Chetana, Madeva ; Venegas, Ana M. ; Sharp, Leslie L. ; Hedrick, Stephen M. ; Fowlkes, B.J. ; Schwartzberg, Pamela L.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c434t-188d3ab00fc0a60c61455efdf0161e64738e7207471d0d320f063b8922f4f88a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Animals</topic><topic>Bone marrow</topic><topic>CD8-Positive T-Lymphocytes - cytology</topic><topic>CD8-Positive T-Lymphocytes - enzymology</topic><topic>CD8-Positive T-Lymphocytes - immunology</topic><topic>Cell Differentiation</topic><topic>Cell Lineage</topic><topic>CELLIMMUNO</topic><topic>DEVBIO</topic><topic>Flow cytometry</topic><topic>Histocompatibility Antigens - metabolism</topic><topic>Immune system</topic><topic>Kinases</topic><topic>Lymphocytes</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Organ Culture Techniques</topic><topic>Peptides</topic><topic>Phenotype</topic><topic>Protein-Tyrosine Kinases - classification</topic><topic>Protein-Tyrosine Kinases - deficiency</topic><topic>Protein-Tyrosine Kinases - genetics</topic><topic>Protein-Tyrosine Kinases - metabolism</topic><topic>Signal Transduction</topic><topic>SIGNALING</topic><topic>T cell receptors</topic><topic>Thymus Gland - cytology</topic><topic>Thymus Gland - immunology</topic><topic>Thymus Gland - metabolism</topic><topic>Time Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Broussard, Christine</creatorcontrib><creatorcontrib>Fleischecker, Christine</creatorcontrib><creatorcontrib>Horai, Reiko</creatorcontrib><creatorcontrib>Chetana, Madeva</creatorcontrib><creatorcontrib>Venegas, Ana M.</creatorcontrib><creatorcontrib>Sharp, Leslie L.</creatorcontrib><creatorcontrib>Hedrick, Stephen M.</creatorcontrib><creatorcontrib>Fowlkes, B.J.</creatorcontrib><creatorcontrib>Schwartzberg, Pamela L.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Immunity (Cambridge, Mass.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Broussard, Christine</au><au>Fleischecker, Christine</au><au>Horai, Reiko</au><au>Chetana, Madeva</au><au>Venegas, Ana M.</au><au>Sharp, Leslie L.</au><au>Hedrick, Stephen M.</au><au>Fowlkes, B.J.</au><au>Schwartzberg, Pamela L.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Altered Development of CD8 + T Cell Lineages in Mice Deficient for the Tec Kinases Itk and Rlk</atitle><jtitle>Immunity (Cambridge, Mass.)</jtitle><addtitle>Immunity</addtitle><date>2006-07-01</date><risdate>2006</risdate><volume>25</volume><issue>1</issue><spage>93</spage><epage>104</epage><pages>93-104</pages><issn>1074-7613</issn><eissn>1097-4180</eissn><abstract>Mutations affecting the Tec kinases Itk and Rlk decrease T cell receptor-induced Ca
2+ mobilization and Erk kinase activation and impair both positive and negative thymic selection.
Itk
−/−
and
Rlk
−/−Itk
−/−
mice also have decreased CD4:8 T cell ratios, suggestive of altered CD4:8 lineage commitment. Nonetheless, we find that CD8 single-positive (SP) thymocytes and peripheral CD8
+ T cells in these mice do not resemble conventional CD8
+ T cells. Instead, these cells express memory markers, rapidly produce interferon-γ, and can be selected on hematopoietically derived cells, similar to MHC class Ib-restricted “innate-type” lymphocytes. Itk deficiency also greatly increases the number of cells selected by MHC class Ib. Expression of a hypersensitive Erk2 mutant partially corrects the CD8
+ T cell phenotypes in
Itk
−/−
mice, arguing that altered signaling permits development of this innate-type CD8
+ cell population. Our results suggest that Tec kinases differentially regulate development of conventional versus nonconventional lymphocytes.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>16860760</pmid><doi>10.1016/j.immuni.2006.05.011</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1074-7613 |
| ispartof | Immunity (Cambridge, Mass.), 2006-07, Vol.25 (1), p.93-104 |
| issn | 1074-7613 1097-4180 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_68668948 |
| source | BACON - Elsevier - GLOBAL_SCIENCEDIRECT-OPENACCESS |
| subjects | Animals Bone marrow CD8-Positive T-Lymphocytes - cytology CD8-Positive T-Lymphocytes - enzymology CD8-Positive T-Lymphocytes - immunology Cell Differentiation Cell Lineage CELLIMMUNO DEVBIO Flow cytometry Histocompatibility Antigens - metabolism Immune system Kinases Lymphocytes Mice Mice, Knockout Organ Culture Techniques Peptides Phenotype Protein-Tyrosine Kinases - classification Protein-Tyrosine Kinases - deficiency Protein-Tyrosine Kinases - genetics Protein-Tyrosine Kinases - metabolism Signal Transduction SIGNALING T cell receptors Thymus Gland - cytology Thymus Gland - immunology Thymus Gland - metabolism Time Factors |
| title | Altered Development of CD8 + T Cell Lineages in Mice Deficient for the Tec Kinases Itk and Rlk |
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