Vaccine-elicited CD4 T cells induce immunopathology after chronic LCMV infection
CD4 T cells promote innate and adaptive immune responses, but how vaccine-elicited CD4 T cells contribute to immune protection remains unclear. We evaluated whether induction of virus-specific CD4 T cells by vaccination would protect mice against infection with chronic lymphocytic choriomeningitis v...
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| Veröffentlicht in: | Science (American Association for the Advancement of Science) 2015-01, Vol.347 (6219), p.278-282 |
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| creator | Penaloza-MacMaster, Pablo Barber, Daniel L. Wherry, E. John Provine, Nicholas M. Teigler, Jeffrey E. Parenteau, Lily Blackmore, Stephen Borducchi, Erica N. Larocca, Rafael A. Yates, Kathleen B. Shen, Hao Haining, W. Nicholas Sommerstein, Rami Pinschewer, Daniel D. Ahmed, Rafi Barouch, Dan H. |
| description | CD4 T cells promote innate and adaptive immune responses, but how vaccine-elicited CD4 T cells contribute to immune protection remains unclear. We evaluated whether induction of virus-specific CD4 T cells by vaccination would protect mice against infection with chronic lymphocytic choriomeningitis virus (LCMV). Immunization with vaccines that selectively induced CD4 T cell responses resulted in catastrophic inflammation and mortality after challenge with a persistent strain of LCMV. Immunopathology required antigen-specific CD4 T cells and was associated with a cytokine storm, generalized inflammation, and multi-organ system failure. Virus-specific CD8 T cells or antibodies abrogated the pathology. These data demonstrate that vaccine-elicited CD4 T cells in the absence of effective antiviral immune responses can trigger lethal immunopathology. |
| doi_str_mv | 10.1126/science.aaa2148 |
| format | Article |
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John ; Provine, Nicholas M. ; Teigler, Jeffrey E. ; Parenteau, Lily ; Blackmore, Stephen ; Borducchi, Erica N. ; Larocca, Rafael A. ; Yates, Kathleen B. ; Shen, Hao ; Haining, W. Nicholas ; Sommerstein, Rami ; Pinschewer, Daniel D. ; Ahmed, Rafi ; Barouch, Dan H.</creator><creatorcontrib>Penaloza-MacMaster, Pablo ; Barber, Daniel L. ; Wherry, E. John ; Provine, Nicholas M. ; Teigler, Jeffrey E. ; Parenteau, Lily ; Blackmore, Stephen ; Borducchi, Erica N. ; Larocca, Rafael A. ; Yates, Kathleen B. ; Shen, Hao ; Haining, W. Nicholas ; Sommerstein, Rami ; Pinschewer, Daniel D. ; Ahmed, Rafi ; Barouch, Dan H.</creatorcontrib><description>CD4 T cells promote innate and adaptive immune responses, but how vaccine-elicited CD4 T cells contribute to immune protection remains unclear. We evaluated whether induction of virus-specific CD4 T cells by vaccination would protect mice against infection with chronic lymphocytic choriomeningitis virus (LCMV). Immunization with vaccines that selectively induced CD4 T cell responses resulted in catastrophic inflammation and mortality after challenge with a persistent strain of LCMV. Immunopathology required antigen-specific CD4 T cells and was associated with a cytokine storm, generalized inflammation, and multi-organ system failure. Virus-specific CD8 T cells or antibodies abrogated the pathology. These data demonstrate that vaccine-elicited CD4 T cells in the absence of effective antiviral immune responses can trigger lethal immunopathology.</description><identifier>ISSN: 0036-8075</identifier><identifier>EISSN: 1095-9203</identifier><identifier>DOI: 10.1126/science.aaa2148</identifier><identifier>PMID: 25593185</identifier><identifier>CODEN: SCIEAS</identifier><language>eng</language><publisher>United States: American Association for the Advancement of Science</publisher><subject>Adaptive Immunity ; Animals ; Antibodies ; Antibodies, Viral - immunology ; Antigens, Viral - immunology ; Arenaviridae Infections - immunology ; Arenaviridae Infections - virology ; CD4-Positive T-Lymphocytes - immunology ; CD8-Positive T-Lymphocytes - immunology ; Cellular biology ; Cytokines ; Cytokines - blood ; Epitopes, T-Lymphocyte - immunology ; Immune system ; Immune System Diseases - etiology ; Immune System Diseases - immunology ; Immune System Diseases - pathology ; Immunologic Memory ; Inflammation - etiology ; Inflammation - immunology ; Inflammation - pathology ; Lentivirus ; Lymphocytes ; Lymphocytic choriomeningitis virus ; Lymphocytic choriomeningitis virus - immunology ; Lymphocytic choriomeningitis virus - physiology ; Memory ; Mice ; Mice, Inbred C57BL ; Mortality ; Multiple Organ Failure - etiology ; Pathology ; Retroviridae ; Storms ; Vaccination ; Vaccines ; Viral infections ; Viral Load ; Viral Vaccines - adverse effects ; Viral Vaccines - immunology ; Virus Replication ; Viruses</subject><ispartof>Science (American Association for the Advancement of Science), 2015-01, Vol.347 (6219), p.278-282</ispartof><rights>Copyright © 2015 American Association for the Advancement of Science</rights><rights>Copyright © 2015, American Association for the Advancement of Science.</rights><rights>Copyright © 2015, American Association for the Advancement of Science</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c454t-d84033ee7dee2452dea69be0127939cdb6747b0fd9392ba2c8e6f13bf44bf82d3</citedby><cites>FETCH-LOGICAL-c454t-d84033ee7dee2452dea69be0127939cdb6747b0fd9392ba2c8e6f13bf44bf82d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/24745879$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/24745879$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>314,776,780,799,2871,2872,27901,27902,57992,58225</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25593185$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Penaloza-MacMaster, Pablo</creatorcontrib><creatorcontrib>Barber, Daniel L.</creatorcontrib><creatorcontrib>Wherry, E. John</creatorcontrib><creatorcontrib>Provine, Nicholas M.</creatorcontrib><creatorcontrib>Teigler, Jeffrey E.</creatorcontrib><creatorcontrib>Parenteau, Lily</creatorcontrib><creatorcontrib>Blackmore, Stephen</creatorcontrib><creatorcontrib>Borducchi, Erica N.</creatorcontrib><creatorcontrib>Larocca, Rafael A.</creatorcontrib><creatorcontrib>Yates, Kathleen B.</creatorcontrib><creatorcontrib>Shen, Hao</creatorcontrib><creatorcontrib>Haining, W. Nicholas</creatorcontrib><creatorcontrib>Sommerstein, Rami</creatorcontrib><creatorcontrib>Pinschewer, Daniel D.</creatorcontrib><creatorcontrib>Ahmed, Rafi</creatorcontrib><creatorcontrib>Barouch, Dan H.</creatorcontrib><title>Vaccine-elicited CD4 T cells induce immunopathology after chronic LCMV infection</title><title>Science (American Association for the Advancement of Science)</title><addtitle>Science</addtitle><description>CD4 T cells promote innate and adaptive immune responses, but how vaccine-elicited CD4 T cells contribute to immune protection remains unclear. We evaluated whether induction of virus-specific CD4 T cells by vaccination would protect mice against infection with chronic lymphocytic choriomeningitis virus (LCMV). Immunization with vaccines that selectively induced CD4 T cell responses resulted in catastrophic inflammation and mortality after challenge with a persistent strain of LCMV. Immunopathology required antigen-specific CD4 T cells and was associated with a cytokine storm, generalized inflammation, and multi-organ system failure. Virus-specific CD8 T cells or antibodies abrogated the pathology. These data demonstrate that vaccine-elicited CD4 T cells in the absence of effective antiviral immune responses can trigger lethal immunopathology.</description><subject>Adaptive Immunity</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Antibodies, Viral - immunology</subject><subject>Antigens, Viral - immunology</subject><subject>Arenaviridae Infections - immunology</subject><subject>Arenaviridae Infections - virology</subject><subject>CD4-Positive T-Lymphocytes - immunology</subject><subject>CD8-Positive T-Lymphocytes - immunology</subject><subject>Cellular biology</subject><subject>Cytokines</subject><subject>Cytokines - blood</subject><subject>Epitopes, T-Lymphocyte - immunology</subject><subject>Immune system</subject><subject>Immune System Diseases - etiology</subject><subject>Immune System Diseases - immunology</subject><subject>Immune System Diseases - pathology</subject><subject>Immunologic Memory</subject><subject>Inflammation - etiology</subject><subject>Inflammation - immunology</subject><subject>Inflammation - pathology</subject><subject>Lentivirus</subject><subject>Lymphocytes</subject><subject>Lymphocytic choriomeningitis virus</subject><subject>Lymphocytic choriomeningitis virus - immunology</subject><subject>Lymphocytic choriomeningitis virus - physiology</subject><subject>Memory</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mortality</subject><subject>Multiple Organ Failure - etiology</subject><subject>Pathology</subject><subject>Retroviridae</subject><subject>Storms</subject><subject>Vaccination</subject><subject>Vaccines</subject><subject>Viral infections</subject><subject>Viral Load</subject><subject>Viral Vaccines - adverse effects</subject><subject>Viral Vaccines - immunology</subject><subject>Virus Replication</subject><subject>Viruses</subject><issn>0036-8075</issn><issn>1095-9203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkTtPwzAQxy0EgvKYmUCRWFgCfib2iMpTKoIBWCPHvoCrJC52MvTb46oFJBZuOZ3ud88_QscEXxBCi8toHPQGLrTWlHC5hSYEK5Eritk2mmDMilziUuyh_RjnGKecYrtoj4rkiRQT9PymjXE95NA64waw2fSaZy-ZgbaNmevtaCBzXTf2fqGHD9_692WmmwFCZj6C753JZtPHt0Q2YAbn-0O00-g2wtHGH6DX25uX6X0-e7p7mF7NcsMFH3IrOWYMoLQAlAtqQReqBkxoqZgyti5KXta4sSmitaZGQtEQVjec142klh2g83XfRfCfI8Sh6lxcba178GOsiMKcUiwk-R-VjFKBpVqhZ3_QuR9Dnw6pSMGFVEWyRF2uKRN8jAGaahFcp8OyIrha6VJtdKk2uqSK003fse7A_vDfQiTgZA3M4-DDb56XaWp6yReum5N8</recordid><startdate>20150116</startdate><enddate>20150116</enddate><creator>Penaloza-MacMaster, Pablo</creator><creator>Barber, Daniel L.</creator><creator>Wherry, E. 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John</au><au>Provine, Nicholas M.</au><au>Teigler, Jeffrey E.</au><au>Parenteau, Lily</au><au>Blackmore, Stephen</au><au>Borducchi, Erica N.</au><au>Larocca, Rafael A.</au><au>Yates, Kathleen B.</au><au>Shen, Hao</au><au>Haining, W. Nicholas</au><au>Sommerstein, Rami</au><au>Pinschewer, Daniel D.</au><au>Ahmed, Rafi</au><au>Barouch, Dan H.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Vaccine-elicited CD4 T cells induce immunopathology after chronic LCMV infection</atitle><jtitle>Science (American Association for the Advancement of Science)</jtitle><addtitle>Science</addtitle><date>2015-01-16</date><risdate>2015</risdate><volume>347</volume><issue>6219</issue><spage>278</spage><epage>282</epage><pages>278-282</pages><issn>0036-8075</issn><eissn>1095-9203</eissn><coden>SCIEAS</coden><abstract>CD4 T cells promote innate and adaptive immune responses, but how vaccine-elicited CD4 T cells contribute to immune protection remains unclear. We evaluated whether induction of virus-specific CD4 T cells by vaccination would protect mice against infection with chronic lymphocytic choriomeningitis virus (LCMV). Immunization with vaccines that selectively induced CD4 T cell responses resulted in catastrophic inflammation and mortality after challenge with a persistent strain of LCMV. Immunopathology required antigen-specific CD4 T cells and was associated with a cytokine storm, generalized inflammation, and multi-organ system failure. Virus-specific CD8 T cells or antibodies abrogated the pathology. These data demonstrate that vaccine-elicited CD4 T cells in the absence of effective antiviral immune responses can trigger lethal immunopathology.</abstract><cop>United States</cop><pub>American Association for the Advancement of Science</pub><pmid>25593185</pmid><doi>10.1126/science.aaa2148</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Science (American Association for the Advancement of Science), 2015-01, Vol.347 (6219), p.278-282 |
| issn | 0036-8075 1095-9203 |
| language | eng |
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| source | American Association for the Advancement of Science; Jstor Complete Legacy; MEDLINE |
| subjects | Adaptive Immunity Animals Antibodies Antibodies, Viral - immunology Antigens, Viral - immunology Arenaviridae Infections - immunology Arenaviridae Infections - virology CD4-Positive T-Lymphocytes - immunology CD8-Positive T-Lymphocytes - immunology Cellular biology Cytokines Cytokines - blood Epitopes, T-Lymphocyte - immunology Immune system Immune System Diseases - etiology Immune System Diseases - immunology Immune System Diseases - pathology Immunologic Memory Inflammation - etiology Inflammation - immunology Inflammation - pathology Lentivirus Lymphocytes Lymphocytic choriomeningitis virus Lymphocytic choriomeningitis virus - immunology Lymphocytic choriomeningitis virus - physiology Memory Mice Mice, Inbred C57BL Mortality Multiple Organ Failure - etiology Pathology Retroviridae Storms Vaccination Vaccines Viral infections Viral Load Viral Vaccines - adverse effects Viral Vaccines - immunology Virus Replication Viruses |
| title | Vaccine-elicited CD4 T cells induce immunopathology after chronic LCMV infection |
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