In a recent study published in Nature,Nobs and colleagues aimed to identify novel mechanisms that may explain why diabetes is associated with an increased susceptibility to viral respiratory infections.Their analyses ...In a recent study published in Nature,Nobs and colleagues aimed to identify novel mechanisms that may explain why diabetes is associated with an increased susceptibility to viral respiratory infections.Their analyses revealed a central role of lung dendritic cells(DC)which exhibited several functional defects induced by hyperglycaemia and consequently result in impaired antiviral immune responses.展开更多
Several obstacles to the production,expansion and genetic modification of immunotherapeutic T cells in vitro have restricted the widespread use of T-cell immunotherapy.In the context of HSCT,delayed naïve T-cell ...Several obstacles to the production,expansion and genetic modification of immunotherapeutic T cells in vitro have restricted the widespread use of T-cell immunotherapy.In the context of HSCT,delayed naïve T-cell recovery contributes to poor outcomes.A novel approach to overcome the major limitations of both T-cell immunotherapy and HSCT would be to transplant human T-lymphoid progenitors(HTLPs),allowing reconstitution of a fully functional naïve T-cell pool in the patient thymus.However,it is challenging to produce HTLPs in the high numbers required to meet clinical needs.Here,we found that adding tumor necrosis factor alpha(TNFα)to a DL-4-based culture system led to the generation of a large number of nonmodified or genetically modified HTLPs possessing highly efficient in vitro and in vivo T-cell potential from either CB HSPCs or mPB HSPCs through accelerated T-cell differentiation and enhanced HTLP cell cycling and survival.This study provides a clinically suitable cell culture platform to generate high numbers of clinically potent nonmodified or genetically modified HTLPs for accelerating immune recovery after HSCT and for T-cell-based immunotherapy(including CAR T-cell therapy).展开更多
基金supported by a grant from Horizon Europe (INTERCEPT-T2D,101095433)supported by the German Diabetes Center (DDZ),which is funded by the German Federal Ministry of Health (Berlin,Germany)+1 种基金the Ministry of Culture and Science of the state North Rhine-Westphalia (Düsseldorf,Germany)receives additional funding from the German Federal Ministry of Education and Research (BMBF)through the German Center for Diabetes Research (DZD e.V.).
文摘In a recent study published in Nature,Nobs and colleagues aimed to identify novel mechanisms that may explain why diabetes is associated with an increased susceptibility to viral respiratory infections.Their analyses revealed a central role of lung dendritic cells(DC)which exhibited several functional defects induced by hyperglycaemia and consequently result in impaired antiviral immune responses.
基金supported by the French Institut National de la Sante et de la Recherche Medicale(INSERM)the European Union Seventh Framework Programme under grant agreements No 269037 and No 261387,the European Unionzs Horizon 2020 research and innovation programme under grant agreement No 666908+1 种基金state funding from the Agence Nationale de la Recherche under the"Investissement d'evenir"program(ANR-10-IAHU-01)the Paris Ile-de-France Region under the"DIM Th^rapie g^niquev initiative.K.M.was funded by the China Scholarship Council and the Fondation pour la Recherche Medicale.A.C.was funded by the French Institut National du Cancer.
文摘Several obstacles to the production,expansion and genetic modification of immunotherapeutic T cells in vitro have restricted the widespread use of T-cell immunotherapy.In the context of HSCT,delayed naïve T-cell recovery contributes to poor outcomes.A novel approach to overcome the major limitations of both T-cell immunotherapy and HSCT would be to transplant human T-lymphoid progenitors(HTLPs),allowing reconstitution of a fully functional naïve T-cell pool in the patient thymus.However,it is challenging to produce HTLPs in the high numbers required to meet clinical needs.Here,we found that adding tumor necrosis factor alpha(TNFα)to a DL-4-based culture system led to the generation of a large number of nonmodified or genetically modified HTLPs possessing highly efficient in vitro and in vivo T-cell potential from either CB HSPCs or mPB HSPCs through accelerated T-cell differentiation and enhanced HTLP cell cycling and survival.This study provides a clinically suitable cell culture platform to generate high numbers of clinically potent nonmodified or genetically modified HTLPs for accelerating immune recovery after HSCT and for T-cell-based immunotherapy(including CAR T-cell therapy).
