NK cells require antigen‐specific memory CD4+ T cells to mediate superior effector functions during HSV‐2 recall responses in vitro
Cross‐talk between HSV‐2‐specific CD4+ T cell and NK cells impacts NK cell function during secondary exposure to HSV‐2 antigens. Natural killer (NK) cells have an important role in mounting protective innate responses against genital herpes simplex virus type 2 (HSV‐2) infections. However their role...
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| Veröffentlicht in: | Journal of leukocyte biology 2017-04, Vol.101 (4), p.1045-1052 |
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| creator | Chen, Branson Lee, Amanda J. Chew, Marianne V. Ashkar, Ali A. |
| description | Cross‐talk between HSV‐2‐specific CD4+ T cell and NK cells impacts NK cell function during secondary exposure to HSV‐2 antigens.
Natural killer (NK) cells have an important role in mounting protective innate responses against genital herpes simplex virus type 2 (HSV‐2) infections. However their role as effectors in adaptive immune responses against HSV‐2 is unclear. Here, we demonstrate that NK cells from C57BL/6 mice in an ex vivo splenocyte culture produce significantly more interferon γ (IFN‐γ) upon re‐exposure to HSV‐2 antigens in a mouse model of genital HSV‐2 immunization. We find that naïve NK cells do not require any prior stimulation or priming to be activated to produce IFN‐γ. Our results demonstrate that HSV‐2–experienced CD4+ T cells have a crucial role in coordinating NK cell activation and that their presence during HSV‐2 antigen presentation is required to activate NK cells in this model of secondary immune response. We also examined the requirement of cell‐to‐cell contacts for both CD4+ T cells and NK cells. NK cells are dependent on direct interactions with other HSV‐2–experienced splenocytes, and CD4+ T cells need to be in close proximity to NK cells to activate them. This study revealed that NK cells do not exhibit any memory toward HSV‐2 antigens and, in fact, require specific interactions with HSV‐2–experienced CD4+ T cells to produce IFN‐γ |
| doi_str_mv | 10.1189/jlb.4A0416-192R |
| format | Article |
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Natural killer (NK) cells have an important role in mounting protective innate responses against genital herpes simplex virus type 2 (HSV‐2) infections. However their role as effectors in adaptive immune responses against HSV‐2 is unclear. Here, we demonstrate that NK cells from C57BL/6 mice in an ex vivo splenocyte culture produce significantly more interferon γ (IFN‐γ) upon re‐exposure to HSV‐2 antigens in a mouse model of genital HSV‐2 immunization. We find that naïve NK cells do not require any prior stimulation or priming to be activated to produce IFN‐γ. Our results demonstrate that HSV‐2–experienced CD4+ T cells have a crucial role in coordinating NK cell activation and that their presence during HSV‐2 antigen presentation is required to activate NK cells in this model of secondary immune response. We also examined the requirement of cell‐to‐cell contacts for both CD4+ T cells and NK cells. NK cells are dependent on direct interactions with other HSV‐2–experienced splenocytes, and CD4+ T cells need to be in close proximity to NK cells to activate them. This study revealed that NK cells do not exhibit any memory toward HSV‐2 antigens and, in fact, require specific interactions with HSV‐2–experienced CD4+ T cells to produce IFN‐γ</description><identifier>ISSN: 0741-5400</identifier><identifier>EISSN: 1938-3673</identifier><identifier>DOI: 10.1189/jlb.4A0416-192R</identifier><identifier>PMID: 27974365</identifier><language>eng</language><publisher>United States: Oxford University Press</publisher><subject>Adaptive immunity ; Animals ; Antigen presentation ; Antigens ; Antigens, Viral - immunology ; CD4 antigen ; CD4-Positive T-Lymphocytes - immunology ; Cell activation ; Cell culture ; Effector cells ; Exposure ; Female ; Herpes simplex ; Herpesviridae ; Herpesvirus 2, Human - immunology ; Immune response ; Immune system ; Immunization ; Immunologic Memory ; Immunological memory ; innate immunity ; Interferon ; interferon γ ; Interferon-gamma - biosynthesis ; Interleukin-2 - secretion ; Killer Cells, Natural - cytology ; Killer Cells, Natural - immunology ; Lymphocyte Activation ; Lymphocyte receptors ; Lymphocytes ; Lymphocytes T ; Memory cells ; Mice, Inbred C57BL ; Natural killer cells ; Priming ; Spleen - cytology ; Splenocytes ; T cell receptors ; Viruses ; γ-Interferon</subject><ispartof>Journal of leukocyte biology, 2017-04, Vol.101 (4), p.1045-1052</ispartof><rights>2017 Society for Leukocyte Biology</rights><rights>Society for Leukocyte Biology.</rights><rights>Copyright Federation of American Societies for Experimental Biology (FASEB) Apr 2017</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4495-c857bfbf8d442dce6368bf02cad5b57709b960aea3b4493fa720b4c122acff03</citedby><cites>FETCH-LOGICAL-c4495-c857bfbf8d442dce6368bf02cad5b57709b960aea3b4493fa720b4c122acff03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1189%2Fjlb.4A0416-192R$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1189%2Fjlb.4A0416-192R$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27923,27924,45573,45574</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27974365$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Branson</creatorcontrib><creatorcontrib>Lee, Amanda J.</creatorcontrib><creatorcontrib>Chew, Marianne V.</creatorcontrib><creatorcontrib>Ashkar, Ali A.</creatorcontrib><title>NK cells require antigen‐specific memory CD4+ T cells to mediate superior effector functions during HSV‐2 recall responses in vitro</title><title>Journal of leukocyte biology</title><addtitle>J Leukoc Biol</addtitle><description>Cross‐talk between HSV‐2‐specific CD4+ T cell and NK cells impacts NK cell function during secondary exposure to HSV‐2 antigens.
Natural killer (NK) cells have an important role in mounting protective innate responses against genital herpes simplex virus type 2 (HSV‐2) infections. However their role as effectors in adaptive immune responses against HSV‐2 is unclear. Here, we demonstrate that NK cells from C57BL/6 mice in an ex vivo splenocyte culture produce significantly more interferon γ (IFN‐γ) upon re‐exposure to HSV‐2 antigens in a mouse model of genital HSV‐2 immunization. We find that naïve NK cells do not require any prior stimulation or priming to be activated to produce IFN‐γ. Our results demonstrate that HSV‐2–experienced CD4+ T cells have a crucial role in coordinating NK cell activation and that their presence during HSV‐2 antigen presentation is required to activate NK cells in this model of secondary immune response. We also examined the requirement of cell‐to‐cell contacts for both CD4+ T cells and NK cells. NK cells are dependent on direct interactions with other HSV‐2–experienced splenocytes, and CD4+ T cells need to be in close proximity to NK cells to activate them. This study revealed that NK cells do not exhibit any memory toward HSV‐2 antigens and, in fact, require specific interactions with HSV‐2–experienced CD4+ T cells to produce IFN‐γ</description><subject>Adaptive immunity</subject><subject>Animals</subject><subject>Antigen presentation</subject><subject>Antigens</subject><subject>Antigens, Viral - immunology</subject><subject>CD4 antigen</subject><subject>CD4-Positive T-Lymphocytes - immunology</subject><subject>Cell activation</subject><subject>Cell culture</subject><subject>Effector cells</subject><subject>Exposure</subject><subject>Female</subject><subject>Herpes simplex</subject><subject>Herpesviridae</subject><subject>Herpesvirus 2, Human - immunology</subject><subject>Immune response</subject><subject>Immune system</subject><subject>Immunization</subject><subject>Immunologic Memory</subject><subject>Immunological memory</subject><subject>innate immunity</subject><subject>Interferon</subject><subject>interferon γ</subject><subject>Interferon-gamma - biosynthesis</subject><subject>Interleukin-2 - secretion</subject><subject>Killer Cells, Natural - cytology</subject><subject>Killer Cells, Natural - immunology</subject><subject>Lymphocyte Activation</subject><subject>Lymphocyte receptors</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Memory cells</subject><subject>Mice, Inbred C57BL</subject><subject>Natural killer cells</subject><subject>Priming</subject><subject>Spleen - cytology</subject><subject>Splenocytes</subject><subject>T cell receptors</subject><subject>Viruses</subject><subject>γ-Interferon</subject><issn>0741-5400</issn><issn>1938-3673</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkT9vFDEQxS0EIkegpkOWaJCiTfx_12VyBAKcQIITreX1jiOf9tYbexd0HR0tn5FPgk93UNBANdb4N2807yH0lJJzSht9senbc3FJBFUV1ezjPbSgmjcVVzW_jxakFrSSgpAT9CjnDSGEM0UeohNW61pwJRfo-_t32EHfZ5zgbg4JsB2mcAvDz28_8ggu-ODwFrYx7fDypTjD6yM-xdLugp0A53mEFGLC4D24qTz8PLgpxCHjbk5huMU3nz4XQVaWONv3peSx_ELGYcBfwpTiY_TA2z7Dk2M9RetX1-vlTbX68PrN8nJVOSG0rFwj69a3vumEYJ0DxVXTesKc7WQr65roVitiwfK28NzbmpFWOMqYdd4TfopeHGTHFO9myJPZhrw_yA4Q52yKp7RRVFL-H6hkqimO7tHnf6GbOKeh3GGobrjgXCpdqIsD5VLMOYE3Ywpbm3aGErNP05Q0zSFNs0-zTDw76s5tMfsP_zu-AogD8DX0sPuXnnm7uqJESP4LwZ-ttg</recordid><startdate>201704</startdate><enddate>201704</enddate><creator>Chen, Branson</creator><creator>Lee, Amanda J.</creator><creator>Chew, Marianne V.</creator><creator>Ashkar, Ali A.</creator><general>Oxford University Press</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>7T5</scope><scope>7T7</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></search><sort><creationdate>201704</creationdate><title>NK cells require antigen‐specific memory CD4+ T cells to mediate superior effector functions during HSV‐2 recall responses in vitro</title><author>Chen, Branson ; Lee, Amanda J. ; Chew, Marianne V. ; Ashkar, Ali A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4495-c857bfbf8d442dce6368bf02cad5b57709b960aea3b4493fa720b4c122acff03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adaptive immunity</topic><topic>Animals</topic><topic>Antigen presentation</topic><topic>Antigens</topic><topic>Antigens, Viral - immunology</topic><topic>CD4 antigen</topic><topic>CD4-Positive T-Lymphocytes - immunology</topic><topic>Cell activation</topic><topic>Cell culture</topic><topic>Effector cells</topic><topic>Exposure</topic><topic>Female</topic><topic>Herpes simplex</topic><topic>Herpesviridae</topic><topic>Herpesvirus 2, Human - immunology</topic><topic>Immune response</topic><topic>Immune system</topic><topic>Immunization</topic><topic>Immunologic Memory</topic><topic>Immunological memory</topic><topic>innate immunity</topic><topic>Interferon</topic><topic>interferon γ</topic><topic>Interferon-gamma - biosynthesis</topic><topic>Interleukin-2 - secretion</topic><topic>Killer Cells, Natural - cytology</topic><topic>Killer Cells, Natural - immunology</topic><topic>Lymphocyte Activation</topic><topic>Lymphocyte receptors</topic><topic>Lymphocytes</topic><topic>Lymphocytes T</topic><topic>Memory cells</topic><topic>Mice, Inbred C57BL</topic><topic>Natural killer cells</topic><topic>Priming</topic><topic>Spleen - cytology</topic><topic>Splenocytes</topic><topic>T cell receptors</topic><topic>Viruses</topic><topic>γ-Interferon</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Branson</creatorcontrib><creatorcontrib>Lee, Amanda J.</creatorcontrib><creatorcontrib>Chew, Marianne V.</creatorcontrib><creatorcontrib>Ashkar, Ali A.</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>Immunology Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</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><jtitle>Journal of leukocyte biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Branson</au><au>Lee, Amanda J.</au><au>Chew, Marianne V.</au><au>Ashkar, Ali A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>NK cells require antigen‐specific memory CD4+ T cells to mediate superior effector functions during HSV‐2 recall responses in vitro</atitle><jtitle>Journal of leukocyte biology</jtitle><addtitle>J Leukoc Biol</addtitle><date>2017-04</date><risdate>2017</risdate><volume>101</volume><issue>4</issue><spage>1045</spage><epage>1052</epage><pages>1045-1052</pages><issn>0741-5400</issn><eissn>1938-3673</eissn><abstract>Cross‐talk between HSV‐2‐specific CD4+ T cell and NK cells impacts NK cell function during secondary exposure to HSV‐2 antigens.
Natural killer (NK) cells have an important role in mounting protective innate responses against genital herpes simplex virus type 2 (HSV‐2) infections. However their role as effectors in adaptive immune responses against HSV‐2 is unclear. Here, we demonstrate that NK cells from C57BL/6 mice in an ex vivo splenocyte culture produce significantly more interferon γ (IFN‐γ) upon re‐exposure to HSV‐2 antigens in a mouse model of genital HSV‐2 immunization. We find that naïve NK cells do not require any prior stimulation or priming to be activated to produce IFN‐γ. Our results demonstrate that HSV‐2–experienced CD4+ T cells have a crucial role in coordinating NK cell activation and that their presence during HSV‐2 antigen presentation is required to activate NK cells in this model of secondary immune response. We also examined the requirement of cell‐to‐cell contacts for both CD4+ T cells and NK cells. NK cells are dependent on direct interactions with other HSV‐2–experienced splenocytes, and CD4+ T cells need to be in close proximity to NK cells to activate them. This study revealed that NK cells do not exhibit any memory toward HSV‐2 antigens and, in fact, require specific interactions with HSV‐2–experienced CD4+ T cells to produce IFN‐γ</abstract><cop>United States</cop><pub>Oxford University Press</pub><pmid>27974365</pmid><doi>10.1189/jlb.4A0416-192R</doi><tpages>8</tpages></addata></record> |
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| source | MEDLINE; Oxford University Press Journals All Titles (1996-Current); EZB-FREE-00999 freely available EZB journals; Wiley Online Library All Journals; Alma/SFX Local Collection |
| subjects | Adaptive immunity Animals Antigen presentation Antigens Antigens, Viral - immunology CD4 antigen CD4-Positive T-Lymphocytes - immunology Cell activation Cell culture Effector cells Exposure Female Herpes simplex Herpesviridae Herpesvirus 2, Human - immunology Immune response Immune system Immunization Immunologic Memory Immunological memory innate immunity Interferon interferon γ Interferon-gamma - biosynthesis Interleukin-2 - secretion Killer Cells, Natural - cytology Killer Cells, Natural - immunology Lymphocyte Activation Lymphocyte receptors Lymphocytes Lymphocytes T Memory cells Mice, Inbred C57BL Natural killer cells Priming Spleen - cytology Splenocytes T cell receptors Viruses γ-Interferon |
| title | NK cells require antigen‐specific memory CD4+ T cells to mediate superior effector functions during HSV‐2 recall responses in vitro |
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