Clonal composition of neuroantigen-specific CD8+ and CD4+ T-cells in multiple sclerosis
Abstract Patients with multiple sclerosis (MS) show a high prevalence of myelin-reactive CD8+ and CD4+ T-cell responses, which are the putative effectors/modulators of CNS neuropathology. Utilizing a novel combination of short-term culture, CFSE-based sorting and anchored PCR, we evaluated clonal co...
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| Veröffentlicht in: | Journal of neuroimmunology 2011-05, Vol.234 (1), p.131-140 |
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| creator | Biegler, Brian W Yan, Shirley X Ortega, Sterling B Tennakoon, Deepani K Racke, Michael K Karandikar, Nitin J |
| description | Abstract Patients with multiple sclerosis (MS) show a high prevalence of myelin-reactive CD8+ and CD4+ T-cell responses, which are the putative effectors/modulators of CNS neuropathology. Utilizing a novel combination of short-term culture, CFSE-based sorting and anchored PCR, we evaluated clonal compositions of neuroantigen-targeting T-cells from RRMS patients and controls. CDR3 region analysis of TCRβ chains revealed biased use of specific TCRBV-bearing CD4+ clones. CD8+ clones showed homology to published TCR from CNS-infiltrating T-cells in MS lesions. These studies are the first description of TCR usage of CNS-specific CD8+ T-cells and provide insights into their potential regulatory role in disease. |
| doi_str_mv | 10.1016/j.jneuroim.2011.02.001 |
| format | Article |
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Utilizing a novel combination of short-term culture, CFSE-based sorting and anchored PCR, we evaluated clonal compositions of neuroantigen-targeting T-cells from RRMS patients and controls. CDR3 region analysis of TCRβ chains revealed biased use of specific TCRBV-bearing CD4+ clones. CD8+ clones showed homology to published TCR from CNS-infiltrating T-cells in MS lesions. These studies are the first description of TCR usage of CNS-specific CD8+ T-cells and provide insights into their potential regulatory role in disease.</description><identifier>ISSN: 0165-5728</identifier><identifier>EISSN: 1872-8421</identifier><identifier>DOI: 10.1016/j.jneuroim.2011.02.001</identifier><identifier>PMID: 21397340</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Adult ; Allergy and Immunology ; Antibodies - metabolism ; CD4 ; CD4-Positive T-Lymphocytes - metabolism ; CD4-Positive T-Lymphocytes - pathology ; CD8 ; CD8-Positive T-Lymphocytes - metabolism ; CD8-Positive T-Lymphocytes - pathology ; CDR3 ; Cloning, Molecular ; Female ; Flow Cytometry - methods ; Humans ; Male ; Middle Aged ; Molecular Sequence Data ; Multiple sclerosis ; Multiple Sclerosis - cerebrospinal fluid ; Multiple Sclerosis - pathology ; Myelin ; Myelin Basic Protein - genetics ; Myelin Basic Protein - metabolism ; Myelin Proteolipid Protein - genetics ; Myelin Proteolipid Protein - metabolism ; Myelin Sheath - immunology ; Neurology ; Receptors, Antigen, T-Cell ; TCR</subject><ispartof>Journal of neuroimmunology, 2011-05, Vol.234 (1), p.131-140</ispartof><rights>Elsevier B.V.</rights><rights>2011 Elsevier B.V.</rights><rights>Copyright © 2011 Elsevier B.V. All rights reserved.</rights><rights>2011 Elsevier B.V. All rights reserved. 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c557t-2c9a4e4f8041511bb136402cd3c90d4f756fc4246f0daa8a3cbebd39f6657adb3</citedby><cites>FETCH-LOGICAL-c557t-2c9a4e4f8041511bb136402cd3c90d4f756fc4246f0daa8a3cbebd39f6657adb3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.jneuroim.2011.02.001$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,780,784,885,3548,27923,27924,45994</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21397340$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Biegler, Brian W</creatorcontrib><creatorcontrib>Yan, Shirley X</creatorcontrib><creatorcontrib>Ortega, Sterling B</creatorcontrib><creatorcontrib>Tennakoon, Deepani K</creatorcontrib><creatorcontrib>Racke, Michael K</creatorcontrib><creatorcontrib>Karandikar, Nitin J</creatorcontrib><title>Clonal composition of neuroantigen-specific CD8+ and CD4+ T-cells in multiple sclerosis</title><title>Journal of neuroimmunology</title><addtitle>J Neuroimmunol</addtitle><description>Abstract Patients with multiple sclerosis (MS) show a high prevalence of myelin-reactive CD8+ and CD4+ T-cell responses, which are the putative effectors/modulators of CNS neuropathology. Utilizing a novel combination of short-term culture, CFSE-based sorting and anchored PCR, we evaluated clonal compositions of neuroantigen-targeting T-cells from RRMS patients and controls. CDR3 region analysis of TCRβ chains revealed biased use of specific TCRBV-bearing CD4+ clones. CD8+ clones showed homology to published TCR from CNS-infiltrating T-cells in MS lesions. These studies are the first description of TCR usage of CNS-specific CD8+ T-cells and provide insights into their potential regulatory role in disease.</description><subject>Adult</subject><subject>Allergy and Immunology</subject><subject>Antibodies - metabolism</subject><subject>CD4</subject><subject>CD4-Positive T-Lymphocytes - metabolism</subject><subject>CD4-Positive T-Lymphocytes - pathology</subject><subject>CD8</subject><subject>CD8-Positive T-Lymphocytes - metabolism</subject><subject>CD8-Positive T-Lymphocytes - pathology</subject><subject>CDR3</subject><subject>Cloning, Molecular</subject><subject>Female</subject><subject>Flow Cytometry - methods</subject><subject>Humans</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Molecular Sequence Data</subject><subject>Multiple sclerosis</subject><subject>Multiple Sclerosis - cerebrospinal fluid</subject><subject>Multiple Sclerosis - pathology</subject><subject>Myelin</subject><subject>Myelin Basic Protein - genetics</subject><subject>Myelin Basic Protein - metabolism</subject><subject>Myelin Proteolipid Protein - genetics</subject><subject>Myelin Proteolipid Protein - metabolism</subject><subject>Myelin Sheath - immunology</subject><subject>Neurology</subject><subject>Receptors, Antigen, T-Cell</subject><subject>TCR</subject><issn>0165-5728</issn><issn>1872-8421</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkktv1TAQhS0EopfCX6iyY1El9TNxNhXolkelSiwoYmk5zqQ4OHawk0r99zjctgI2XdmSvzmeOWcQOiG4IpjUZ2M1elhjsFNFMSEVphXG5BnaEdnQUnJKnqNdBkUpGiqP0KuUxgwIxtuX6IgS1jaM4x36vnfBa1eYMM0h2cUGX4Sh-KOt_WJvwJdpBmMHa4r9hTwttO_zhZ8W16UB51JhfTGtbrGzgyIZBzHrpNfoxaBdgjf35zH69vHD9f5zefXl0-X-_VVphGiWkppWc-CDxJwIQrqOsJpjanpmWtzzoRH1YDjl9YB7raVmpoOuZ-1Q16LRfceO0flBd167CXoDfonaqTnaScc7FbRV_754-0PdhFvFcEul4Fng7b1ADL9WSIuabNoG0x7CmpSUDPM6G_c0WddUYEnaTNYH0mQvUoThsR-C1RafGtVDfGqLT2Gqcjq58OTvaR7LHvLKwLsDANnTWwtRJWPBG-htBLOoPtin_zj_T8I4663R7ifcQRrDGvNCJEVUygXq67ZE2w4RgjGmomG_AcYRxQE</recordid><startdate>20110501</startdate><enddate>20110501</enddate><creator>Biegler, Brian W</creator><creator>Yan, Shirley X</creator><creator>Ortega, Sterling B</creator><creator>Tennakoon, Deepani K</creator><creator>Racke, Michael K</creator><creator>Karandikar, Nitin J</creator><general>Elsevier B.V</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>7X8</scope><scope>7T5</scope><scope>7TK</scope><scope>H94</scope><scope>5PM</scope></search><sort><creationdate>20110501</creationdate><title>Clonal composition of neuroantigen-specific CD8+ and CD4+ T-cells in multiple sclerosis</title><author>Biegler, Brian W ; Yan, Shirley X ; Ortega, Sterling B ; Tennakoon, Deepani K ; Racke, Michael K ; Karandikar, Nitin J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c557t-2c9a4e4f8041511bb136402cd3c90d4f756fc4246f0daa8a3cbebd39f6657adb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Adult</topic><topic>Allergy and Immunology</topic><topic>Antibodies - metabolism</topic><topic>CD4</topic><topic>CD4-Positive T-Lymphocytes - metabolism</topic><topic>CD4-Positive T-Lymphocytes - pathology</topic><topic>CD8</topic><topic>CD8-Positive T-Lymphocytes - metabolism</topic><topic>CD8-Positive T-Lymphocytes - pathology</topic><topic>CDR3</topic><topic>Cloning, Molecular</topic><topic>Female</topic><topic>Flow Cytometry - methods</topic><topic>Humans</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Molecular Sequence Data</topic><topic>Multiple sclerosis</topic><topic>Multiple Sclerosis - cerebrospinal fluid</topic><topic>Multiple Sclerosis - pathology</topic><topic>Myelin</topic><topic>Myelin Basic Protein - genetics</topic><topic>Myelin Basic Protein - metabolism</topic><topic>Myelin Proteolipid Protein - genetics</topic><topic>Myelin Proteolipid Protein - metabolism</topic><topic>Myelin Sheath - immunology</topic><topic>Neurology</topic><topic>Receptors, Antigen, T-Cell</topic><topic>TCR</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Biegler, Brian W</creatorcontrib><creatorcontrib>Yan, Shirley X</creatorcontrib><creatorcontrib>Ortega, Sterling B</creatorcontrib><creatorcontrib>Tennakoon, Deepani K</creatorcontrib><creatorcontrib>Racke, Michael K</creatorcontrib><creatorcontrib>Karandikar, Nitin J</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of neuroimmunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Biegler, Brian W</au><au>Yan, Shirley X</au><au>Ortega, Sterling B</au><au>Tennakoon, Deepani K</au><au>Racke, Michael K</au><au>Karandikar, Nitin J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Clonal composition of neuroantigen-specific CD8+ and CD4+ T-cells in multiple sclerosis</atitle><jtitle>Journal of neuroimmunology</jtitle><addtitle>J Neuroimmunol</addtitle><date>2011-05-01</date><risdate>2011</risdate><volume>234</volume><issue>1</issue><spage>131</spage><epage>140</epage><pages>131-140</pages><issn>0165-5728</issn><eissn>1872-8421</eissn><abstract>Abstract Patients with multiple sclerosis (MS) show a high prevalence of myelin-reactive CD8+ and CD4+ T-cell responses, which are the putative effectors/modulators of CNS neuropathology. Utilizing a novel combination of short-term culture, CFSE-based sorting and anchored PCR, we evaluated clonal compositions of neuroantigen-targeting T-cells from RRMS patients and controls. CDR3 region analysis of TCRβ chains revealed biased use of specific TCRBV-bearing CD4+ clones. CD8+ clones showed homology to published TCR from CNS-infiltrating T-cells in MS lesions. These studies are the first description of TCR usage of CNS-specific CD8+ T-cells and provide insights into their potential regulatory role in disease.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>21397340</pmid><doi>10.1016/j.jneuroim.2011.02.001</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| language | eng |
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| subjects | Adult Allergy and Immunology Antibodies - metabolism CD4 CD4-Positive T-Lymphocytes - metabolism CD4-Positive T-Lymphocytes - pathology CD8 CD8-Positive T-Lymphocytes - metabolism CD8-Positive T-Lymphocytes - pathology CDR3 Cloning, Molecular Female Flow Cytometry - methods Humans Male Middle Aged Molecular Sequence Data Multiple sclerosis Multiple Sclerosis - cerebrospinal fluid Multiple Sclerosis - pathology Myelin Myelin Basic Protein - genetics Myelin Basic Protein - metabolism Myelin Proteolipid Protein - genetics Myelin Proteolipid Protein - metabolism Myelin Sheath - immunology Neurology Receptors, Antigen, T-Cell TCR |
| title | Clonal composition of neuroantigen-specific CD8+ and CD4+ T-cells in multiple sclerosis |
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