Premium
Overexpression of Jagged‐1 combined with blockade of CD40 pathway prolongs allograft survival
Author(s) -
Lin Yingying,
Chen Weili,
Li Jiali,
Yan Guoliang,
Li Chun,
Jin Ning,
Chen Jie,
Gao Chang,
Ma Pengfei,
Xu Shuangyue,
Qi Zhongquan
Publication year - 2015
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1038/icb.2014.84
Subject(s) - jag1 , blockade , cd40 , immunology , transplantation , monoclonal antibody , immune system , medicine , population , heart transplantation , immune tolerance , t cell , stimulation , downregulation and upregulation , dendritic cell , cancer research , antibody , biology , microbiology and biotechnology , notch signaling pathway , signal transduction , receptor , gene , cytotoxic t cell , environmental health , biochemistry , in vitro
Dendritic cells (DCs) have the tolerogenic potential to regulate adaptive immunity and induce allografts acceptance. Here we investigated whether blockade of the CD40 pathway could enhance the immune tolerance induced by DC2.4 cells modified to express Jagged‐1 (JAG1‐DC) in heart transplantation. Results showed that JAG1‐DC treatment combined with anti‐CD40L monoclonal antibody (mAb) administration significantly prolonged cardiac allograft survival in mice, with long‐term survival (>110 days) of 50% of the allografts in the recipients. The therapy specifically inhibited the immune response, induced alloantigen‐specific T‐cell hyporesponsiveness, upregulated transforming growth factor‐β synthesis and increased the population of regulatory T cells (Tregs) driven by Jagged‐1‐Notch activation. These results highlight the potential application of gene therapy to induce alloantigen‐specific Tregs effectively by providing the Jagged‐1 stimulation.