Enhanced humoral and HLA‐A2‐restricted dengue virus‐specific T‐cell responses in humanized BLT NSG mice
Summary Dengue is a mosquito‐borne viral disease of humans, and animal models that recapitulate human immune responses or dengue pathogenesis are needed to understand the pathogenesis of the disease. We recently described an animal model for dengue virus (DENV) infection using humanized NOD‐scid IL2...
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Veröffentlicht in: | Immunology 2012-07, Vol.136 (3), p.334-343 |
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creator | Jaiswal, Smita Pazoles, Pamela Woda, Marcia Shultz, Leonard D. Greiner, Dale L. Brehm, Michael A. Mathew, Anuja |
description | Summary
Dengue is a mosquito‐borne viral disease of humans, and animal models that recapitulate human immune responses or dengue pathogenesis are needed to understand the pathogenesis of the disease. We recently described an animal model for dengue virus (DENV) infection using humanized NOD‐scid IL2rγnull mice (NSG) engrafted with cord blood haematopoietic stem cells. We sought to further improve this model by co‐transplantation of human fetal thymus and liver tissues into NSG (BLT‐NSG) mice. Enhanced DENV‐specific antibody titres were found in the sera of BLT‐NSG mice compared with human cord blood haematopoietic stem cell‐engrafted NSG mice. Furthermore, B cells generated during the acute phase and in memory from splenocytes of immunized BLT‐NSG mice secreted DENV‐specific IgM antibodies with neutralizing activity. Human T cells in engrafted BLT‐NSG mice secreted interferon‐γ in response to overlapping DENV peptide pools and HLA‐A2 restricted peptides. The BLT‐NSG mice will allow assessment of human immune responses to DENV vaccines and the effects of previous immunity on subsequent DENV infections. |
doi_str_mv | 10.1111/j.1365-2567.2012.03585.x |
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Dengue is a mosquito‐borne viral disease of humans, and animal models that recapitulate human immune responses or dengue pathogenesis are needed to understand the pathogenesis of the disease. We recently described an animal model for dengue virus (DENV) infection using humanized NOD‐scid IL2rγnull mice (NSG) engrafted with cord blood haematopoietic stem cells. We sought to further improve this model by co‐transplantation of human fetal thymus and liver tissues into NSG (BLT‐NSG) mice. Enhanced DENV‐specific antibody titres were found in the sera of BLT‐NSG mice compared with human cord blood haematopoietic stem cell‐engrafted NSG mice. Furthermore, B cells generated during the acute phase and in memory from splenocytes of immunized BLT‐NSG mice secreted DENV‐specific IgM antibodies with neutralizing activity. Human T cells in engrafted BLT‐NSG mice secreted interferon‐γ in response to overlapping DENV peptide pools and HLA‐A2 restricted peptides. The BLT‐NSG mice will allow assessment of human immune responses to DENV vaccines and the effects of previous immunity on subsequent DENV infections.</description><identifier>ISSN: 0019-2805</identifier><identifier>EISSN: 1365-2567</identifier><identifier>DOI: 10.1111/j.1365-2567.2012.03585.x</identifier><identifier>PMID: 22384859</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Animals ; Antibodies, Neutralizing - blood ; Antibodies, Viral - blood ; Antibody Specificity ; B-Lymphocytes - immunology ; B-Lymphocytes - virology ; Base Sequence ; dengue ; Dengue - immunology ; Dengue - prevention & control ; Dengue - virology ; Dengue fever ; Dengue Vaccines - immunology ; Dengue Virus - genetics ; Dengue Virus - immunology ; Fetal Tissue Transplantation ; HLA-A2 Antigen - metabolism ; human ; Humans ; Immunity, Humoral ; Interferon-gamma - biosynthesis ; Liver Transplantation ; Medical research ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Original ; Pathogenesis ; RNA, Viral - blood ; RNA, Viral - genetics ; Stem cells ; T cells ; T-Lymphocytes - immunology ; T-Lymphocytes - virology ; Thymus Gland - transplantation ; transgenic mice ; viral ; Viral Load</subject><ispartof>Immunology, 2012-07, Vol.136 (3), p.334-343</ispartof><rights>2012 The Authors. Immunology © 2012 Blackwell Publishing Ltd</rights><rights>2012 The Authors. Immunology © 2012 Blackwell Publishing Ltd.</rights><rights>2012 The Authors. Immunology © 2012 Blackwell Publishing Ltd 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5025-f6a687525387e053d7af0137d469365ad847d66bf03643669e62e3000bd0df1f3</citedby><cites>FETCH-LOGICAL-c5025-f6a687525387e053d7af0137d469365ad847d66bf03643669e62e3000bd0df1f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3385033/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3385033/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,1411,1427,27903,27904,45553,45554,46388,46812,53770,53772</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22384859$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jaiswal, Smita</creatorcontrib><creatorcontrib>Pazoles, Pamela</creatorcontrib><creatorcontrib>Woda, Marcia</creatorcontrib><creatorcontrib>Shultz, Leonard D.</creatorcontrib><creatorcontrib>Greiner, Dale L.</creatorcontrib><creatorcontrib>Brehm, Michael A.</creatorcontrib><creatorcontrib>Mathew, Anuja</creatorcontrib><title>Enhanced humoral and HLA‐A2‐restricted dengue virus‐specific T‐cell responses in humanized BLT NSG mice</title><title>Immunology</title><addtitle>Immunology</addtitle><description>Summary
Dengue is a mosquito‐borne viral disease of humans, and animal models that recapitulate human immune responses or dengue pathogenesis are needed to understand the pathogenesis of the disease. We recently described an animal model for dengue virus (DENV) infection using humanized NOD‐scid IL2rγnull mice (NSG) engrafted with cord blood haematopoietic stem cells. We sought to further improve this model by co‐transplantation of human fetal thymus and liver tissues into NSG (BLT‐NSG) mice. Enhanced DENV‐specific antibody titres were found in the sera of BLT‐NSG mice compared with human cord blood haematopoietic stem cell‐engrafted NSG mice. Furthermore, B cells generated during the acute phase and in memory from splenocytes of immunized BLT‐NSG mice secreted DENV‐specific IgM antibodies with neutralizing activity. Human T cells in engrafted BLT‐NSG mice secreted interferon‐γ in response to overlapping DENV peptide pools and HLA‐A2 restricted peptides. The BLT‐NSG mice will allow assessment of human immune responses to DENV vaccines and the effects of previous immunity on subsequent DENV infections.</description><subject>Animals</subject><subject>Antibodies, Neutralizing - blood</subject><subject>Antibodies, Viral - blood</subject><subject>Antibody Specificity</subject><subject>B-Lymphocytes - immunology</subject><subject>B-Lymphocytes - virology</subject><subject>Base Sequence</subject><subject>dengue</subject><subject>Dengue - immunology</subject><subject>Dengue - prevention & control</subject><subject>Dengue - virology</subject><subject>Dengue fever</subject><subject>Dengue Vaccines - immunology</subject><subject>Dengue Virus - genetics</subject><subject>Dengue Virus - immunology</subject><subject>Fetal Tissue Transplantation</subject><subject>HLA-A2 Antigen - metabolism</subject><subject>human</subject><subject>Humans</subject><subject>Immunity, Humoral</subject><subject>Interferon-gamma - biosynthesis</subject><subject>Liver Transplantation</subject><subject>Medical research</subject><subject>Mice</subject><subject>Mice, Inbred NOD</subject><subject>Mice, SCID</subject><subject>Original</subject><subject>Pathogenesis</subject><subject>RNA, Viral - blood</subject><subject>RNA, Viral - genetics</subject><subject>Stem cells</subject><subject>T cells</subject><subject>T-Lymphocytes - immunology</subject><subject>T-Lymphocytes - virology</subject><subject>Thymus Gland - transplantation</subject><subject>transgenic mice</subject><subject>viral</subject><subject>Viral Load</subject><issn>0019-2805</issn><issn>1365-2567</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkc1uEzEUhS1ERUPhFZAlNmxm6p-xx1mAFKrSVkphQVhbju1pHM14gp0pLSsegWfkSXqnaaPCCi_8o_vdo3t8EMKUlBTW8bqkXIqCCVmXjFBWEi6UKG-eocm-8BxNCKHTgikiDtHLnNfw5ESIF-iQMa4qJaYT1J_GlYnWO7wauj6ZFpvo8Pl89ufX7xmDLfm8TcFugXA-Xg0eX4c0ZKjkjbehCRYv4GF922JgN33MPuMQRz0Tw0_o-zhf4M9fz3AXrH-FDhrTZv_64TxC3z6dLk7Oi_mXs4uT2bywgjBRNNJIVQsmuKo9EdzVpoHpa1fJKRg0TlW1k3LZEC4rLuXUS-Y5IWTpiGtow4_Qh53uZlh23lkft2BOb1LoTLrVvQn670oMK33VX2vOlSCcg8C7B4HUfx_gE3QX8ujSRN8PWVP4W0mFlBTQt_-g635IEexpKipJaiVqBpTaUTb1OSff7IehRI-p6rUew9NjeHpMVd-nqm-g9c1TM_vGxxgBeL8DfoTW3_63sL64vBxv_A40R7PL</recordid><startdate>201207</startdate><enddate>201207</enddate><creator>Jaiswal, Smita</creator><creator>Pazoles, Pamela</creator><creator>Woda, Marcia</creator><creator>Shultz, Leonard D.</creator><creator>Greiner, Dale L.</creator><creator>Brehm, Michael A.</creator><creator>Mathew, Anuja</creator><general>Blackwell Publishing Ltd</general><general>Wiley Subscription Services, Inc</general><general>Blackwell Science Inc</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>7QL</scope><scope>7QR</scope><scope>7T5</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>201207</creationdate><title>Enhanced humoral and HLA‐A2‐restricted dengue virus‐specific T‐cell responses in humanized BLT NSG mice</title><author>Jaiswal, Smita ; Pazoles, Pamela ; Woda, Marcia ; Shultz, Leonard D. ; Greiner, Dale L. ; Brehm, Michael A. ; Mathew, Anuja</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5025-f6a687525387e053d7af0137d469365ad847d66bf03643669e62e3000bd0df1f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Animals</topic><topic>Antibodies, Neutralizing - blood</topic><topic>Antibodies, Viral - blood</topic><topic>Antibody Specificity</topic><topic>B-Lymphocytes - immunology</topic><topic>B-Lymphocytes - virology</topic><topic>Base Sequence</topic><topic>dengue</topic><topic>Dengue - immunology</topic><topic>Dengue - prevention & control</topic><topic>Dengue - virology</topic><topic>Dengue fever</topic><topic>Dengue Vaccines - immunology</topic><topic>Dengue Virus - genetics</topic><topic>Dengue Virus - immunology</topic><topic>Fetal Tissue Transplantation</topic><topic>HLA-A2 Antigen - metabolism</topic><topic>human</topic><topic>Humans</topic><topic>Immunity, Humoral</topic><topic>Interferon-gamma - biosynthesis</topic><topic>Liver Transplantation</topic><topic>Medical research</topic><topic>Mice</topic><topic>Mice, Inbred NOD</topic><topic>Mice, SCID</topic><topic>Original</topic><topic>Pathogenesis</topic><topic>RNA, Viral - blood</topic><topic>RNA, Viral - genetics</topic><topic>Stem cells</topic><topic>T cells</topic><topic>T-Lymphocytes - immunology</topic><topic>T-Lymphocytes - virology</topic><topic>Thymus Gland - transplantation</topic><topic>transgenic mice</topic><topic>viral</topic><topic>Viral Load</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jaiswal, Smita</creatorcontrib><creatorcontrib>Pazoles, Pamela</creatorcontrib><creatorcontrib>Woda, Marcia</creatorcontrib><creatorcontrib>Shultz, Leonard D.</creatorcontrib><creatorcontrib>Greiner, Dale L.</creatorcontrib><creatorcontrib>Brehm, Michael A.</creatorcontrib><creatorcontrib>Mathew, Anuja</creatorcontrib><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>Chemoreception Abstracts</collection><collection>Immunology 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>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jaiswal, Smita</au><au>Pazoles, Pamela</au><au>Woda, Marcia</au><au>Shultz, Leonard D.</au><au>Greiner, Dale L.</au><au>Brehm, Michael A.</au><au>Mathew, Anuja</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Enhanced humoral and HLA‐A2‐restricted dengue virus‐specific T‐cell responses in humanized BLT NSG mice</atitle><jtitle>Immunology</jtitle><addtitle>Immunology</addtitle><date>2012-07</date><risdate>2012</risdate><volume>136</volume><issue>3</issue><spage>334</spage><epage>343</epage><pages>334-343</pages><issn>0019-2805</issn><eissn>1365-2567</eissn><abstract>Summary
Dengue is a mosquito‐borne viral disease of humans, and animal models that recapitulate human immune responses or dengue pathogenesis are needed to understand the pathogenesis of the disease. We recently described an animal model for dengue virus (DENV) infection using humanized NOD‐scid IL2rγnull mice (NSG) engrafted with cord blood haematopoietic stem cells. We sought to further improve this model by co‐transplantation of human fetal thymus and liver tissues into NSG (BLT‐NSG) mice. Enhanced DENV‐specific antibody titres were found in the sera of BLT‐NSG mice compared with human cord blood haematopoietic stem cell‐engrafted NSG mice. Furthermore, B cells generated during the acute phase and in memory from splenocytes of immunized BLT‐NSG mice secreted DENV‐specific IgM antibodies with neutralizing activity. Human T cells in engrafted BLT‐NSG mice secreted interferon‐γ in response to overlapping DENV peptide pools and HLA‐A2 restricted peptides. The BLT‐NSG mice will allow assessment of human immune responses to DENV vaccines and the effects of previous immunity on subsequent DENV infections.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>22384859</pmid><doi>10.1111/j.1365-2567.2012.03585.x</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Animals Antibodies, Neutralizing - blood Antibodies, Viral - blood Antibody Specificity B-Lymphocytes - immunology B-Lymphocytes - virology Base Sequence dengue Dengue - immunology Dengue - prevention & control Dengue - virology Dengue fever Dengue Vaccines - immunology Dengue Virus - genetics Dengue Virus - immunology Fetal Tissue Transplantation HLA-A2 Antigen - metabolism human Humans Immunity, Humoral Interferon-gamma - biosynthesis Liver Transplantation Medical research Mice Mice, Inbred NOD Mice, SCID Original Pathogenesis RNA, Viral - blood RNA, Viral - genetics Stem cells T cells T-Lymphocytes - immunology T-Lymphocytes - virology Thymus Gland - transplantation transgenic mice viral Viral Load |
title | Enhanced humoral and HLA‐A2‐restricted dengue virus‐specific T‐cell responses in humanized BLT NSG mice |
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