Superior induction and maintenance of protective CD8 T cells in mice infected with mouse cytomegalovirus vector expressing RAE-1γ
Due to a unique pattern of CD8 T-cell response induced by cytomegaloviruses (CMVs), live attenuated CMVs are attractive candidates for vaccine vectors for a number of clinically relevant infections and tumors. NKG2D is one of the most important activating NK cell receptors that plays a role in costi...
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creator | Tršan, Tihana Busche, Andreas Abram, Maja Wensveen, Felix M. Lemmermann, Niels A. Arapović, Maja Babić, Marina Tomić, Adriana Golemac, Mijo Brinkmann, Melanie M. Jäger, Wiebke Oxenius, Annette Polić, Bojan Krmpotić, Astrid Messerle, Martin Jonjić, Stipan |
description | Due to a unique pattern of CD8 T-cell response induced by cytomegaloviruses (CMVs), live attenuated CMVs are attractive candidates for vaccine vectors for a number of clinically relevant infections and tumors. NKG2D is one of the most important activating NK cell receptors that plays a role in costimulation of CD8 T cells. Here we demonstrate that the expression of CD8 T-cell epitope of Listeria monocytogenes by a recombinant mouse CMV (MCMV) expressing the NKG2D ligand retinoic acid early-inducible protein 1-gamma (RAE-1γ) dramatically enhanced the effectiveness and longevity of epitope-specific CD8 T-cell response and conferred protection against a subsequent challenge infection with Listeria monocytogenes . Unexpectedly, the attenuated growth in vivo of the CMV vector expressing RAE-1γ and its capacity to enhance specific CD8 T-cell response were preserved even in mice lacking NKG2D, implying additional immune function for RAE-1γ beyond engagement of NKG2D. Thus, vectors expressing RAE-1γ represent a promising approach in the development of CD8 T-cell–based vaccines. |
doi_str_mv | 10.1073/pnas.1310215110 |
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NKG2D is one of the most important activating NK cell receptors that plays a role in costimulation of CD8 T cells. Here we demonstrate that the expression of CD8 T-cell epitope of Listeria monocytogenes by a recombinant mouse CMV (MCMV) expressing the NKG2D ligand retinoic acid early-inducible protein 1-gamma (RAE-1γ) dramatically enhanced the effectiveness and longevity of epitope-specific CD8 T-cell response and conferred protection against a subsequent challenge infection with Listeria monocytogenes . Unexpectedly, the attenuated growth in vivo of the CMV vector expressing RAE-1γ and its capacity to enhance specific CD8 T-cell response were preserved even in mice lacking NKG2D, implying additional immune function for RAE-1γ beyond engagement of NKG2D. Thus, vectors expressing RAE-1γ represent a promising approach in the development of CD8 T-cell–based vaccines.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.1310215110</identifier><identifier>PMID: 24052528</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Animals ; Biological Sciences ; CD8-positive T-lymphocytes ; CD8-Positive T-Lymphocytes - immunology ; Cross priming ; Cytomegalovirus ; Cytomegalovirus - genetics ; Cytomegalovirus - immunology ; Epitopes ; Flow Cytometry ; Genetic Vectors - genetics ; Genetic Vectors - immunology ; Immune Evasion - immunology ; Infections ; Listeria monocytogenes ; Listeria monocytogenes - immunology ; listeriosis ; longevity ; Membrane Proteins - genetics ; Membrane Proteins - metabolism ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Knockout ; Murid betaherpesvirus 1 ; Murine cytomegalovirus ; neoplasms ; NK Cell Lectin-Like Receptor Subfamily K - genetics ; Receptors ; retinoic acid ; Spleen ; Statistics, Nonparametric ; T lymphocytes ; Vaccination ; vaccines ; Vaccines, Synthetic - immunology ; Viruses</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2013-10, Vol.110 (41), p.16550-16555</ispartof><rights>copyright © 1993–2008 National Academy of Sciences of the United States of America</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c460t-30b10440096ef2491ed44bebbe65ec6a85f9117b1e360592b24346244075419f3</citedby><cites>FETCH-LOGICAL-c460t-30b10440096ef2491ed44bebbe65ec6a85f9117b1e360592b24346244075419f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/110/41.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/23749560$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/23749560$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,723,776,780,799,881,27901,27902,53766,53768,57992,58225</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24052528$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tršan, Tihana</creatorcontrib><creatorcontrib>Busche, Andreas</creatorcontrib><creatorcontrib>Abram, Maja</creatorcontrib><creatorcontrib>Wensveen, Felix M.</creatorcontrib><creatorcontrib>Lemmermann, Niels A.</creatorcontrib><creatorcontrib>Arapović, Maja</creatorcontrib><creatorcontrib>Babić, Marina</creatorcontrib><creatorcontrib>Tomić, Adriana</creatorcontrib><creatorcontrib>Golemac, Mijo</creatorcontrib><creatorcontrib>Brinkmann, Melanie M.</creatorcontrib><creatorcontrib>Jäger, Wiebke</creatorcontrib><creatorcontrib>Oxenius, Annette</creatorcontrib><creatorcontrib>Polić, Bojan</creatorcontrib><creatorcontrib>Krmpotić, Astrid</creatorcontrib><creatorcontrib>Messerle, Martin</creatorcontrib><creatorcontrib>Jonjić, Stipan</creatorcontrib><title>Superior induction and maintenance of protective CD8 T cells in mice infected with mouse cytomegalovirus vector expressing RAE-1γ</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>Due to a unique pattern of CD8 T-cell response induced by cytomegaloviruses (CMVs), live attenuated CMVs are attractive candidates for vaccine vectors for a number of clinically relevant infections and tumors. NKG2D is one of the most important activating NK cell receptors that plays a role in costimulation of CD8 T cells. Here we demonstrate that the expression of CD8 T-cell epitope of Listeria monocytogenes by a recombinant mouse CMV (MCMV) expressing the NKG2D ligand retinoic acid early-inducible protein 1-gamma (RAE-1γ) dramatically enhanced the effectiveness and longevity of epitope-specific CD8 T-cell response and conferred protection against a subsequent challenge infection with Listeria monocytogenes . Unexpectedly, the attenuated growth in vivo of the CMV vector expressing RAE-1γ and its capacity to enhance specific CD8 T-cell response were preserved even in mice lacking NKG2D, implying additional immune function for RAE-1γ beyond engagement of NKG2D. Thus, vectors expressing RAE-1γ represent a promising approach in the development of CD8 T-cell–based vaccines.</description><subject>Animals</subject><subject>Biological Sciences</subject><subject>CD8-positive T-lymphocytes</subject><subject>CD8-Positive T-Lymphocytes - immunology</subject><subject>Cross priming</subject><subject>Cytomegalovirus</subject><subject>Cytomegalovirus - genetics</subject><subject>Cytomegalovirus - immunology</subject><subject>Epitopes</subject><subject>Flow Cytometry</subject><subject>Genetic Vectors - genetics</subject><subject>Genetic Vectors - immunology</subject><subject>Immune Evasion - immunology</subject><subject>Infections</subject><subject>Listeria monocytogenes</subject><subject>Listeria monocytogenes - immunology</subject><subject>listeriosis</subject><subject>longevity</subject><subject>Membrane Proteins - genetics</subject><subject>Membrane Proteins - metabolism</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Murid betaherpesvirus 1</subject><subject>Murine cytomegalovirus</subject><subject>neoplasms</subject><subject>NK Cell Lectin-Like Receptor Subfamily K - genetics</subject><subject>Receptors</subject><subject>retinoic acid</subject><subject>Spleen</subject><subject>Statistics, Nonparametric</subject><subject>T lymphocytes</subject><subject>Vaccination</subject><subject>vaccines</subject><subject>Vaccines, Synthetic - immunology</subject><subject>Viruses</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFks1u1DAUhSMEokNhzQrwkk3ae_2XeINUDeVHqoRE27XlZJypq4kd7GSgW16J9-CZcDTDFFZdZXG-c5xjn6J4iXCCULHTwZt0ggyBokCER8UCQWEpuYLHxQKAVmXNKT8qnqV0CwBK1PC0OKIcBBW0XhQ_L6fBRhcicX41taMLnhi_Ir1xfrTe-NaS0JEhhtFmdWvJ8n1NrkhrN5uUPaR3mXC-y6pdke9uvCF9mJIl7d0Yers2m7B1cUpkm4l8jP0xRJuS82vy9ey8xN-_nhdPOrNJ9sX-e1xcfzi_Wn4qL758_Lw8uyhbLmEsGTQInOcO0naUK7QrzhvbNFYK20pTi04hVg1aJkEo2lDOuKTZUQmOqmPHxbtd7jA1vV211o_RbPQQXW_inQ7G6f8V7270Omw1q5RidZ0D3u4DYvg22TTq3qX5Ioy3ubLGGhhSqKl6GOWSC8DZ8TCaewBTrMro6Q5tY0gp2u7w8wh63oOe96Dv95Adr__tfOD_DiADZA_MzkNczuOoUQoxZ7zaIbcpP-B9BKu4EnLW3-z0zgRt1tElfX1JASUAcmRUsj9Gq897</recordid><startdate>20131008</startdate><enddate>20131008</enddate><creator>Tršan, Tihana</creator><creator>Busche, Andreas</creator><creator>Abram, Maja</creator><creator>Wensveen, Felix M.</creator><creator>Lemmermann, Niels A.</creator><creator>Arapović, Maja</creator><creator>Babić, Marina</creator><creator>Tomić, Adriana</creator><creator>Golemac, Mijo</creator><creator>Brinkmann, Melanie M.</creator><creator>Jäger, Wiebke</creator><creator>Oxenius, Annette</creator><creator>Polić, Bojan</creator><creator>Krmpotić, Astrid</creator><creator>Messerle, Martin</creator><creator>Jonjić, Stipan</creator><general>National Academy of Sciences</general><general>NATIONAL ACADEMY OF SCIENCES</general><general>National Acad Sciences</general><scope>FBQ</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>7X8</scope><scope>7T5</scope><scope>7U9</scope><scope>H94</scope><scope>7S9</scope><scope>L.6</scope><scope>5PM</scope></search><sort><creationdate>20131008</creationdate><title>Superior induction and maintenance of protective CD8 T cells in mice infected with mouse cytomegalovirus vector expressing RAE-1γ</title><author>Tršan, Tihana ; Busche, Andreas ; Abram, Maja ; Wensveen, Felix M. ; Lemmermann, Niels A. ; Arapović, Maja ; Babić, Marina ; Tomić, Adriana ; Golemac, Mijo ; Brinkmann, Melanie M. ; Jäger, Wiebke ; Oxenius, Annette ; Polić, Bojan ; Krmpotić, Astrid ; Messerle, Martin ; Jonjić, Stipan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c460t-30b10440096ef2491ed44bebbe65ec6a85f9117b1e360592b24346244075419f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Animals</topic><topic>Biological Sciences</topic><topic>CD8-positive T-lymphocytes</topic><topic>CD8-Positive T-Lymphocytes - immunology</topic><topic>Cross priming</topic><topic>Cytomegalovirus</topic><topic>Cytomegalovirus - genetics</topic><topic>Cytomegalovirus - immunology</topic><topic>Epitopes</topic><topic>Flow Cytometry</topic><topic>Genetic Vectors - genetics</topic><topic>Genetic Vectors - immunology</topic><topic>Immune Evasion - immunology</topic><topic>Infections</topic><topic>Listeria monocytogenes</topic><topic>Listeria monocytogenes - immunology</topic><topic>listeriosis</topic><topic>longevity</topic><topic>Membrane Proteins - genetics</topic><topic>Membrane Proteins - metabolism</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Murid betaherpesvirus 1</topic><topic>Murine cytomegalovirus</topic><topic>neoplasms</topic><topic>NK Cell Lectin-Like Receptor Subfamily K - genetics</topic><topic>Receptors</topic><topic>retinoic acid</topic><topic>Spleen</topic><topic>Statistics, Nonparametric</topic><topic>T lymphocytes</topic><topic>Vaccination</topic><topic>vaccines</topic><topic>Vaccines, Synthetic - immunology</topic><topic>Viruses</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tršan, Tihana</creatorcontrib><creatorcontrib>Busche, Andreas</creatorcontrib><creatorcontrib>Abram, Maja</creatorcontrib><creatorcontrib>Wensveen, Felix M.</creatorcontrib><creatorcontrib>Lemmermann, Niels A.</creatorcontrib><creatorcontrib>Arapović, Maja</creatorcontrib><creatorcontrib>Babić, Marina</creatorcontrib><creatorcontrib>Tomić, Adriana</creatorcontrib><creatorcontrib>Golemac, Mijo</creatorcontrib><creatorcontrib>Brinkmann, Melanie M.</creatorcontrib><creatorcontrib>Jäger, Wiebke</creatorcontrib><creatorcontrib>Oxenius, Annette</creatorcontrib><creatorcontrib>Polić, Bojan</creatorcontrib><creatorcontrib>Krmpotić, Astrid</creatorcontrib><creatorcontrib>Messerle, Martin</creatorcontrib><creatorcontrib>Jonjić, Stipan</creatorcontrib><collection>AGRIS</collection><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>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tršan, Tihana</au><au>Busche, Andreas</au><au>Abram, Maja</au><au>Wensveen, Felix M.</au><au>Lemmermann, Niels A.</au><au>Arapović, Maja</au><au>Babić, Marina</au><au>Tomić, Adriana</au><au>Golemac, Mijo</au><au>Brinkmann, Melanie M.</au><au>Jäger, Wiebke</au><au>Oxenius, Annette</au><au>Polić, Bojan</au><au>Krmpotić, Astrid</au><au>Messerle, Martin</au><au>Jonjić, Stipan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Superior induction and maintenance of protective CD8 T cells in mice infected with mouse cytomegalovirus vector expressing RAE-1γ</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>2013-10-08</date><risdate>2013</risdate><volume>110</volume><issue>41</issue><spage>16550</spage><epage>16555</epage><pages>16550-16555</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><abstract>Due to a unique pattern of CD8 T-cell response induced by cytomegaloviruses (CMVs), live attenuated CMVs are attractive candidates for vaccine vectors for a number of clinically relevant infections and tumors. NKG2D is one of the most important activating NK cell receptors that plays a role in costimulation of CD8 T cells. Here we demonstrate that the expression of CD8 T-cell epitope of Listeria monocytogenes by a recombinant mouse CMV (MCMV) expressing the NKG2D ligand retinoic acid early-inducible protein 1-gamma (RAE-1γ) dramatically enhanced the effectiveness and longevity of epitope-specific CD8 T-cell response and conferred protection against a subsequent challenge infection with Listeria monocytogenes . Unexpectedly, the attenuated growth in vivo of the CMV vector expressing RAE-1γ and its capacity to enhance specific CD8 T-cell response were preserved even in mice lacking NKG2D, implying additional immune function for RAE-1γ beyond engagement of NKG2D. Thus, vectors expressing RAE-1γ represent a promising approach in the development of CD8 T-cell–based vaccines.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>24052528</pmid><doi>10.1073/pnas.1310215110</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Animals Biological Sciences CD8-positive T-lymphocytes CD8-Positive T-Lymphocytes - immunology Cross priming Cytomegalovirus Cytomegalovirus - genetics Cytomegalovirus - immunology Epitopes Flow Cytometry Genetic Vectors - genetics Genetic Vectors - immunology Immune Evasion - immunology Infections Listeria monocytogenes Listeria monocytogenes - immunology listeriosis longevity Membrane Proteins - genetics Membrane Proteins - metabolism Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Knockout Murid betaherpesvirus 1 Murine cytomegalovirus neoplasms NK Cell Lectin-Like Receptor Subfamily K - genetics Receptors retinoic acid Spleen Statistics, Nonparametric T lymphocytes Vaccination vaccines Vaccines, Synthetic - immunology Viruses |
title | Superior induction and maintenance of protective CD8 T cells in mice infected with mouse cytomegalovirus vector expressing RAE-1γ |
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