Vadim A. Klenchin, Natasha M. Clark, Nida K. Keles, Saverio Capuano, Rosemarie Mason, Guangping Gao, Aimee Broman, Emek Kose, Taina T. Immonen, Christine M. Fennessey, Brandon F. Keele, Jeffrey D. Lifson, Mario Roederer, Matthew R. Gardner, David T. Evans
{"title":"Adeno-associated viral delivery of Env-specific antibodies prevents SIV rebound after discontinuing antiretroviral therapy","authors":"Vadim A. Klenchin, Natasha M. Clark, Nida K. Keles, Saverio Capuano, Rosemarie Mason, Guangping Gao, Aimee Broman, Emek Kose, Taina T. Immonen, Christine M. Fennessey, Brandon F. Keele, Jeffrey D. Lifson, Mario Roederer, Matthew R. Gardner, David T. Evans","doi":"10.1126/sciimmunol.adq4973","DOIUrl":"https://doi.org/10.1126/sciimmunol.adq4973","url":null,"abstract":"An alternative to lifelong antiretroviral therapy (ART) is needed to achieve durable control of HIV-1. Here, we show that adeno-associated virus (AAV) delivery of two rhesus macaque antibodies to the simian immunodeficiency virus (SIV) envelope glycoprotein (Env) with potent neutralization and antibody-dependent cellular cytotoxicity can prevent viral rebound in macaques infected with barcoded SIV <jats:sub>mac</jats:sub> 239M after discontinuing suppressive ART. After AAV administration, sustained antibody expression with minimal antidrug antibody responses was achieved in all but one animal. After ART withdrawal, SIV replication rebounded within 2 weeks in all control animals but remained <15 copies per milliliter in plasma for more than a year in four of the eight animals that received AAV vectors encoding Env-specific antibodies. Viral sequences from animals that rebounded with delayed kinetics exhibited restricted clonal diversity and antibody escape mutations in Env. Thus, sustained expression of antibodies with potent antiviral activity can afford durable, ART-free containment of pathogenic SIV infection.","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"85 1","pages":""},"PeriodicalIF":24.8,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143518147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Vadim A. Klenchin, Natasha M. Clark, Nida K. Keles, Saverio Capuano III, Rosemarie Mason, Guangping Gao, Aimee Broman, Emek Kose, Taina T. Immonen, Christine M. Fennessey, Brandon F. Keele, Jeffrey D. Lifson, Mario Roederer, Matthew R. Gardner, David T. Evans
{"title":"Adeno-associated viral delivery of Env-specific antibodies prevents SIV rebound after discontinuing antiretroviral therapy","authors":"Vadim A. Klenchin, Natasha M. Clark, Nida K. Keles, Saverio Capuano III, Rosemarie Mason, Guangping Gao, Aimee Broman, Emek Kose, Taina T. Immonen, Christine M. Fennessey, Brandon F. Keele, Jeffrey D. Lifson, Mario Roederer, Matthew R. Gardner, David T. Evans","doi":"","DOIUrl":"","url":null,"abstract":"<div >An alternative to lifelong antiretroviral therapy (ART) is needed to achieve durable control of HIV-1. Here, we show that adeno-associated virus (AAV) delivery of two rhesus macaque antibodies to the simian immunodeficiency virus (SIV) envelope glycoprotein (Env) with potent neutralization and antibody-dependent cellular cytotoxicity can prevent viral rebound in macaques infected with barcoded SIV<sub>mac</sub>239M after discontinuing suppressive ART. After AAV administration, sustained antibody expression with minimal antidrug antibody responses was achieved in all but one animal. After ART withdrawal, SIV replication rebounded within 2 weeks in all control animals but remained <15 copies per milliliter in plasma for more than a year in four of the eight animals that received AAV vectors encoding Env-specific antibodies. Viral sequences from animals that rebounded with delayed kinetics exhibited restricted clonal diversity and antibody escape mutations in Env. Thus, sustained expression of antibodies with potent antiviral activity can afford durable, ART-free containment of pathogenic SIV infection.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"10 104","pages":""},"PeriodicalIF":17.6,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciimmunol.adq4973","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143527749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Joona Sarkkinen, Dawit A. Yohannes, Nea Kreivi, Pia Dürnsteiner, Alexandra Elsakova, Jani Huuhtanen, Kirsten Nowlan, Goran Kurdo, Riikka Linden, Mika Saarela, Pentti J. Tienari, Eliisa Kekäläinen, Maria Perdomo, Sini M. Laakso
{"title":"Altered immune landscape of cervical lymph nodes reveals Epstein-Barr virus signature in multiple sclerosis","authors":"Joona Sarkkinen, Dawit A. Yohannes, Nea Kreivi, Pia Dürnsteiner, Alexandra Elsakova, Jani Huuhtanen, Kirsten Nowlan, Goran Kurdo, Riikka Linden, Mika Saarela, Pentti J. Tienari, Eliisa Kekäläinen, Maria Perdomo, Sini M. Laakso","doi":"10.1126/sciimmunol.adl3604","DOIUrl":"https://doi.org/10.1126/sciimmunol.adl3604","url":null,"abstract":"Multiple sclerosis (MS) is an autoimmune disease of the central nervous system, and Epstein-Barr virus (EBV) infection is a prerequisite for developing the disease. However, the pathogenic mechanisms that lead to MS remain to be determined. Here, we characterized the immune landscape of deep cervical lymph nodes (dcLNs) in newly diagnosed untreated patients with MS (pwMS) using fine-needle aspirations. By combining single-cell RNA sequencing and cellular indexing of transcriptomes and epitopes by sequencing, we observed increased memory B cells and reduced germinal center B cells with decreased clonality in pwMS. Double-negative memory B cells were increased in pwMS that transcriptionally resembled B cells with a lytic EBV infection. Moreover, EBV-targeting memory CD8 T cells were detected in a subset of pwMS. We also detected increased EBV DNA in dcLNs and elevated viral loads in patient saliva. These findings suggest that EBV-driven B cell dysregulation is a critical mechanism in MS pathogenesis.","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"29 1","pages":""},"PeriodicalIF":24.8,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143463192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Justin B. Zhang, Priyanka Chaurasia, Angela Nguyen, Zijian Huang, Trang T. Nguyen, Hui Xu, Mai T. Tran, Hugh H. Reid, Claerwen M. Jones, Stefan A. Schattgen, Daniel Thiele, Paul G. Thomas, Jeanette Rientjes, Kim L. Good-Jacobson, Roland Ruscher, Dene R. Littler, Jamie Rossjohn, Pirooz Zareie, Nicole L. La Gruta
{"title":"LCK–co-receptor association ensures T cell lineage fidelity and maximizes epitope-specific TCR diversity","authors":"Justin B. Zhang, Priyanka Chaurasia, Angela Nguyen, Zijian Huang, Trang T. Nguyen, Hui Xu, Mai T. Tran, Hugh H. Reid, Claerwen M. Jones, Stefan A. Schattgen, Daniel Thiele, Paul G. Thomas, Jeanette Rientjes, Kim L. Good-Jacobson, Roland Ruscher, Dene R. Littler, Jamie Rossjohn, Pirooz Zareie, Nicole L. La Gruta","doi":"10.1126/sciimmunol.adp5016","DOIUrl":"https://doi.org/10.1126/sciimmunol.adp5016","url":null,"abstract":"The interaction between the CD4/CD8 co-receptors and LCK (an Src family tyrosine kinase) is thought to augment T cell activation upon recognition of peptide-loaded major histocompatibility complexes (pMHCs). How this interaction influences antigen-specific T cell development is unclear however, as is its impact on naïve and immune antigen-specific T cell repertoires. In mice expressing mutated endogenous LCK unable to bind co-receptors (LCK <jats:sup>FREE</jats:sup> mice), we show that influenza A virus (IAV)–derived pMHC-specific CD8 and CD4 T cell responses had a significantly narrowed T cell receptor (TCR) repertoire, favoring high-affinity TCRs. This narrowing was established during T cell development and was exacerbated after viral infection. The dissociation of LCK from co-receptors also resulted in the redirection of CD4-fated T cells to the CD8 lineage, with expanded pMHCII-specific cytotoxic CD8 T cells observed after IAV infection. Thus, LCK–co-receptor association is critical for ensuring T cell lineage fidelity and maximizing antigen-specific T cell repertoire diversity.","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"24 1","pages":""},"PeriodicalIF":24.8,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143463092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Joona Sarkkinen, Dawit A. Yohannes, Nea Kreivi, Pia Dürnsteiner, Alexandra Elsakova, Jani Huuhtanen, Kirsten Nowlan, Goran Kurdo, Riikka Linden, Mika Saarela, Pentti J. Tienari, Eliisa Kekäläinen, Maria Perdomo, Sini M. Laakso
{"title":"Altered immune landscape of cervical lymph nodes reveals Epstein-Barr virus signature in multiple sclerosis","authors":"Joona Sarkkinen, Dawit A. Yohannes, Nea Kreivi, Pia Dürnsteiner, Alexandra Elsakova, Jani Huuhtanen, Kirsten Nowlan, Goran Kurdo, Riikka Linden, Mika Saarela, Pentti J. Tienari, Eliisa Kekäläinen, Maria Perdomo, Sini M. Laakso","doi":"","DOIUrl":"","url":null,"abstract":"<div >Multiple sclerosis (MS) is an autoimmune disease of the central nervous system, and Epstein-Barr virus (EBV) infection is a prerequisite for developing the disease. However, the pathogenic mechanisms that lead to MS remain to be determined. Here, we characterized the immune landscape of deep cervical lymph nodes (dcLNs) in newly diagnosed untreated patients with MS (pwMS) using fine-needle aspirations. By combining single-cell RNA sequencing and cellular indexing of transcriptomes and epitopes by sequencing, we observed increased memory B cells and reduced germinal center B cells with decreased clonality in pwMS. Double-negative memory B cells were increased in pwMS that transcriptionally resembled B cells with a lytic EBV infection. Moreover, EBV-targeting memory CD8 T cells were detected in a subset of pwMS. We also detected increased EBV DNA in dcLNs and elevated viral loads in patient saliva. These findings suggest that EBV-driven B cell dysregulation is a critical mechanism in MS pathogenesis.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"10 104","pages":""},"PeriodicalIF":17.6,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Justin B. Zhang, Priyanka Chaurasia, Angela Nguyen, Zijian Huang, Trang T. Nguyen, Hui Xu, Mai T. Tran, Hugh H. Reid, Claerwen M. Jones, Stefan A. Schattgen, Daniel Thiele, Paul G. Thomas, Jeanette Rientjes, Kim L. Good-Jacobson, Roland Ruscher, Dene R. Littler, Jamie Rossjohn, Pirooz Zareie, Nicole L. La Gruta
{"title":"LCK–co-receptor association ensures T cell lineage fidelity and maximizes epitope-specific TCR diversity","authors":"Justin B. Zhang, Priyanka Chaurasia, Angela Nguyen, Zijian Huang, Trang T. Nguyen, Hui Xu, Mai T. Tran, Hugh H. Reid, Claerwen M. Jones, Stefan A. Schattgen, Daniel Thiele, Paul G. Thomas, Jeanette Rientjes, Kim L. Good-Jacobson, Roland Ruscher, Dene R. Littler, Jamie Rossjohn, Pirooz Zareie, Nicole L. La Gruta","doi":"","DOIUrl":"","url":null,"abstract":"<div >The interaction between the CD4/CD8 co-receptors and LCK (an Src family tyrosine kinase) is thought to augment T cell activation upon recognition of peptide-loaded major histocompatibility complexes (pMHCs). How this interaction influences antigen-specific T cell development is unclear however, as is its impact on naïve and immune antigen-specific T cell repertoires. In mice expressing mutated endogenous LCK unable to bind co-receptors (LCK<sup>FREE</sup> mice), we show that influenza A virus (IAV)–derived pMHC-specific CD8 and CD4 T cell responses had a significantly narrowed T cell receptor (TCR) repertoire, favoring high-affinity TCRs. This narrowing was established during T cell development and was exacerbated after viral infection. The dissociation of LCK from co-receptors also resulted in the redirection of CD4-fated T cells to the CD8 lineage, with expanded pMHCII-specific cytotoxic CD8 T cells observed after IAV infection. Thus, LCK–co-receptor association is critical for ensuring T cell lineage fidelity and maximizing antigen-specific T cell repertoire diversity.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"10 104","pages":""},"PeriodicalIF":17.6,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciimmunol.adp5016","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Peng Shao, Regina M. Antonetti, Tina Arkee, Emma L. Hornick, Hai Hui Xue, Gail A. Bishop, Noah S. Butler
{"title":"TRAF3 is critical for initial T follicular helper cell specification via coordination of the IL-6R/IL-2R–BCL6 signaling nexus","authors":"Peng Shao, Regina M. Antonetti, Tina Arkee, Emma L. Hornick, Hai Hui Xue, Gail A. Bishop, Noah S. Butler","doi":"","DOIUrl":"","url":null,"abstract":"<div >CD4<sup>+</sup> T follicular helper (T<sub>FH</sub>) cells are essential for orchestrating robust humoral immunity, yet the signals that initiate T<sub>FH</sub> cell differentiation are not fully understood. We identified that the adapter protein TRAF3 was required for T<sub>FH</sub> cell differentiation and function during systemic inflammatory infections. Loss of CD4<sup>+</sup> T cell–intrinsic TRAF3 impaired chromatin remodeling and transcriptional programming essential for T<sub>FH</sub> cell initiation and instead augmented T<sub>H</sub>1 development and function. TRAF3-deficient CD4<sup>+</sup> T cells exhibited altered interleukin-6 (IL-6) and IL-2 responsiveness, which were coupled to failures in BCL6 expression. Enforced expression of either IL-6 receptor or BCL6 or blockade of IL-2 signaling was sufficient to rescue T<sub>FH</sub> cell differentiation. Human CD4<sup>+</sup> T cells lacking TRAF3 exhibited impaired T<sub>FH</sub> polarization, supporting a conserved mechanism by which TRAF3 regulates CD4<sup>+</sup> T cell fate determination. Thus, TRAF3 functions at the nexus of cytokine, transcriptional, and epigenetic nodes that promote the T<sub>FH</sub> cell specification during infection.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"10 104","pages":""},"PeriodicalIF":17.6,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143424394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Linking vaccine adjuvant mechanisms of action to function.","authors":"Elana Ben-Akiva, Asheley Chapman, Tianyang Mao, Darrell J Irvine","doi":"10.1126/sciimmunol.ado5937","DOIUrl":"10.1126/sciimmunol.ado5937","url":null,"abstract":"<p><p>Vaccines deliver an immunogen in a manner designed to safely provoke an immune response, leading to the generation of memory T and B cells and long-lived antibody-producing plasma cells. Adjuvants play a critical role in vaccines by controlling how the immune system is exposed to the immunogen and providing inflammatory cues that enable productive immune priming. However, mechanisms of action underlying adjuvant function at the molecular, cell, and tissue levels are diverse and often poorly understood. Here, we review the current understanding of mechanisms of action underlying adjuvants used in subunit protein/polysaccharide vaccines and mRNA vaccines, discuss where possible how these mechanisms of action link to downstream effects on the immune response, and identify knowledge gaps that will be important to fill in order to enable the continued development of more effective adjuvants for challenging pathogens such as HIV and emerging threats.</p>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"10 104","pages":"eado5937"},"PeriodicalIF":17.6,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143417149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Peng Shao, Regina M Antonetti, Tina Arkee, Emma L Hornick, Hai Hui Xue, Gail A Bishop, Noah S Butler
{"title":"TRAF3 is critical for initial T follicular helper cell specification via coordination of the IL-6R/IL-2R-BCL6 signaling nexus.","authors":"Peng Shao, Regina M Antonetti, Tina Arkee, Emma L Hornick, Hai Hui Xue, Gail A Bishop, Noah S Butler","doi":"10.1126/sciimmunol.adr0517","DOIUrl":"10.1126/sciimmunol.adr0517","url":null,"abstract":"<p><p>CD4<sup>+</sup> T follicular helper (T<sub>FH</sub>) cells are essential for orchestrating robust humoral immunity, yet the signals that initiate T<sub>FH</sub> cell differentiation are not fully understood. We identified that the adapter protein TRAF3 was required for T<sub>FH</sub> cell differentiation and function during systemic inflammatory infections. Loss of CD4<sup>+</sup> T cell-intrinsic TRAF3 impaired chromatin remodeling and transcriptional programming essential for T<sub>FH</sub> cell initiation and instead augmented T<sub>H</sub>1 development and function. TRAF3-deficient CD4<sup>+</sup> T cells exhibited altered interleukin-6 (IL-6) and IL-2 responsiveness, which were coupled to failures in BCL6 expression. Enforced expression of either IL-6 receptor or BCL6 or blockade of IL-2 signaling was sufficient to rescue T<sub>FH</sub> cell differentiation. Human CD4<sup>+</sup> T cells lacking TRAF3 exhibited impaired T<sub>FH</sub> polarization, supporting a conserved mechanism by which TRAF3 regulates CD4<sup>+</sup> T cell fate determination. Thus, TRAF3 functions at the nexus of cytokine, transcriptional, and epigenetic nodes that promote the T<sub>FH</sub> cell specification during infection.</p>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"10 104","pages":"eadr0517"},"PeriodicalIF":17.6,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143417150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Elana Ben-Akiva, Asheley Chapman, Tianyang Mao, Darrell J. Irvine
{"title":"Linking vaccine adjuvant mechanisms of action to function","authors":"Elana Ben-Akiva, Asheley Chapman, Tianyang Mao, Darrell J. Irvine","doi":"","DOIUrl":"","url":null,"abstract":"<div >Vaccines deliver an immunogen in a manner designed to safely provoke an immune response, leading to the generation of memory T and B cells and long-lived antibody-producing plasma cells. Adjuvants play a critical role in vaccines by controlling how the immune system is exposed to the immunogen and providing inflammatory cues that enable productive immune priming. However, mechanisms of action underlying adjuvant function at the molecular, cell, and tissue levels are diverse and often poorly understood. Here, we review the current understanding of mechanisms of action underlying adjuvants used in subunit protein/polysaccharide vaccines and mRNA vaccines, discuss where possible how these mechanisms of action link to downstream effects on the immune response, and identify knowledge gaps that will be important to fill in order to enable the continued development of more effective adjuvants for challenging pathogens such as HIV and emerging threats.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"10 104","pages":""},"PeriodicalIF":17.6,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143424387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
