Temporal and spatial expression of cosignaling receptors and their ligands regulates the early stages of T-cell activation(signal 1,T-cell receptor(TCR)signaling and signal 2,costimulation/coinhibition),clonal expansi...Temporal and spatial expression of cosignaling receptors and their ligands regulates the early stages of T-cell activation(signal 1,T-cell receptor(TCR)signaling and signal 2,costimulation/coinhibition),clonal expansion and T-cell survival during their differentiation towards effector T cells.Once the inflammatory stimulus is eliminated,effector T cells return to homeostasis after undergoing a contraction phase by activation-induced cell death and the intervention of ligands for coinhibitory receptors,leaving a population of long-term memory T cells.The expression of ligands for coinhibitory receptors on hematopoietic cells and,more importantly,on non-hematopoietic cells of peripheral tissues is a key process in tuning the functional activity of effector T cells to prevent excess tissue inflammation that may lead to immunopathology and subsequent tissue dysfunction.展开更多
The molecular pathways contributing to humoral-mediated allograft rejection are poorly defined. In this study, we assessed the role of the herpesvirus entry mediator/B- and T-lymphocyte attenuator （HVEM/BTLA） signal...The molecular pathways contributing to humoral-mediated allograft rejection are poorly defined. In this study, we assessed the role of the herpesvirus entry mediator/B- and T-lymphocyte attenuator （HVEM/BTLA） signalling pathway in the context of antibody-mediated allograft rejection. An experimental setting was designed to elucidate whether the blockade of HVEM/BTLA interactions could modulate de novo induction of host antidonor-specific antibodies during the course of graft rejection. To test this hypothesis, fully allogeneic major histocompatibility complex-mismatched skin grafts were transplanted onto the right flank of recipient mice that were treated with isotype control, anti-CD40L or modulatory antibodies of the HVEM/BTLA signalling pathway. The frequencies of CD4 T follicular helper （Tfh） cells （B220-, CD4＋ CXCR5＋ PD-lhigh）, extrafollicular helper cells （B220-, CD4＋ CXCR5- PD-1＋ and PD-1-） and germinal centre （GC） B cells （B220＋Fas＋ GL7＋） were analysed by flow cytometry in draining and non-draining lymph nodes at day 10 post transplantation during the acute phase of graft rejection. The host antidonor isotype-specific humoral immune response was also assessed. Whereas blockade of the CD40/CD40L pathway was highly effective in preventing the allogeneic humoral immune response, antibody-mediated blockade of the HVEM/BTLA-interacting pathway affected neither the expansion of Tfh cells nor the expansion of GC B cells. Consequently, the course of the host antidonor antibody-mediated response proceeded normally, without detectable evidence of impaired development. In summary, these data indicate that HVEM/BTLA interactions are dispensable for the formation of de novo host antidonor isotype-specific antibodies in transplantation.展开更多
In this article,one of the grating agencies requested us to incorporate the information,Spanish Government and co-funded by European Union ERDF/ESF,“Investing in your future”,in the acknowledgments section.The corre...In this article,one of the grating agencies requested us to incorporate the information,Spanish Government and co-funded by European Union ERDF/ESF,“Investing in your future”,in the acknowledgments section.The correct acknowledgement is as follows:“This work has been supported by grants of the Spanish Ministry of Health(Fondo de Investigaciones Sanitarias,PI13/00029,Spanish Government and co-funded by European Union ERDF/ESF,“Investing in your future”),Department of Education of Castilla and Leon Regional Government(Grant#LE093U13)and Mutua Madrileña Foundation(Basic research grants 2012)to J.I.R.B.;by Miguel Servet National Program(Ministry of National Health)CP12/03063 and by Gerencia Regional de Salud GRS963/A/2014 to M.L.R.G.We are particularly grateful to Mr.Leonides Alaiz for outstanding animal husbandry.”The authors regret the errors.展开更多
基金grant FIS PI#13/00029(Fondo de Investigaciones Sanitarias,Ministry of Health,Spanish Government and cofunded by the European Union ERDF/ESF,“Investing in your future”)LE093U13 and Unit of Excellence Research UIC#012(Department of Education of the Regional Government,Junta de Castilla y Leon)+3 种基金Gerencia Regional de Salud(BIO/01/15)which were awarded to J.I.R.B.Miguel Servet National Grant(Health National Organization Research)CP12/03063,CPII17/00002 and FIS PI16/00002(Instituto de Salud Carlos III and cofunded by European Union ERDF/ESF,“Investing in your future”)Gerencia Regional de Salud GRS963/A/2014,GRS1142/A/2015 and GRS1505/A/2017 funded the research of M.L.R.G.The National Network CIBERONC(Oncology Research Program,referenced as CB16/12/00480)also cofunded this work.P.S.is funded by grant 31003A-176356 of the Swiss National Science Foundation.A.W.is funded by the grants Deutsche Krebshilfe(70112451)Deutsche Forschungsgemeinschaft(SFB1039,and FOR2438).
文摘Temporal and spatial expression of cosignaling receptors and their ligands regulates the early stages of T-cell activation(signal 1,T-cell receptor(TCR)signaling and signal 2,costimulation/coinhibition),clonal expansion and T-cell survival during their differentiation towards effector T cells.Once the inflammatory stimulus is eliminated,effector T cells return to homeostasis after undergoing a contraction phase by activation-induced cell death and the intervention of ligands for coinhibitory receptors,leaving a population of long-term memory T cells.The expression of ligands for coinhibitory receptors on hematopoietic cells and,more importantly,on non-hematopoietic cells of peripheral tissues is a key process in tuning the functional activity of effector T cells to prevent excess tissue inflammation that may lead to immunopathology and subsequent tissue dysfunction.
文摘The molecular pathways contributing to humoral-mediated allograft rejection are poorly defined. In this study, we assessed the role of the herpesvirus entry mediator/B- and T-lymphocyte attenuator （HVEM/BTLA） signalling pathway in the context of antibody-mediated allograft rejection. An experimental setting was designed to elucidate whether the blockade of HVEM/BTLA interactions could modulate de novo induction of host antidonor-specific antibodies during the course of graft rejection. To test this hypothesis, fully allogeneic major histocompatibility complex-mismatched skin grafts were transplanted onto the right flank of recipient mice that were treated with isotype control, anti-CD40L or modulatory antibodies of the HVEM/BTLA signalling pathway. The frequencies of CD4 T follicular helper （Tfh） cells （B220-, CD4＋ CXCR5＋ PD-lhigh）, extrafollicular helper cells （B220-, CD4＋ CXCR5- PD-1＋ and PD-1-） and germinal centre （GC） B cells （B220＋Fas＋ GL7＋） were analysed by flow cytometry in draining and non-draining lymph nodes at day 10 post transplantation during the acute phase of graft rejection. The host antidonor isotype-specific humoral immune response was also assessed. Whereas blockade of the CD40/CD40L pathway was highly effective in preventing the allogeneic humoral immune response, antibody-mediated blockade of the HVEM/BTLA-interacting pathway affected neither the expansion of Tfh cells nor the expansion of GC B cells. Consequently, the course of the host antidonor antibody-mediated response proceeded normally, without detectable evidence of impaired development. In summary, these data indicate that HVEM/BTLA interactions are dispensable for the formation of de novo host antidonor isotype-specific antibodies in transplantation.
文摘In this article,one of the grating agencies requested us to incorporate the information,Spanish Government and co-funded by European Union ERDF/ESF,“Investing in your future”,in the acknowledgments section.The correct acknowledgement is as follows:“This work has been supported by grants of the Spanish Ministry of Health(Fondo de Investigaciones Sanitarias,PI13/00029,Spanish Government and co-funded by European Union ERDF/ESF,“Investing in your future”),Department of Education of Castilla and Leon Regional Government(Grant#LE093U13)and Mutua Madrileña Foundation(Basic research grants 2012)to J.I.R.B.;by Miguel Servet National Program(Ministry of National Health)CP12/03063 and by Gerencia Regional de Salud GRS963/A/2014 to M.L.R.G.We are particularly grateful to Mr.Leonides Alaiz for outstanding animal husbandry.”The authors regret the errors.
