Immunogenicity and immunomodulatory effects of the human chondrocytes, hChonJ

BMC Musculoskeletal Disorders

Research Article

Myung Chul Lee¹  Bumsup Lee²  Heonsik Choi²  Sujeong Kim²  Jong-Ho Cho²  Yeon-Ju Lee²  Chae-Lyul Lim³ 

[1] Department of Orthopaedic Surgery, Seoul National University College of Medicine, Seoul, Korea;Institute of BioInnovation Research, Kolon Life Science, Inc., Gasan-dong, Geumcheon-gu, Seoul, Korea;Institute of BioInnovation Research, Kolon Life Science, Inc., Gasan-dong, Geumcheon-gu, Seoul, Korea;Present Address: T Cell Therapy Unit, Eutilex Research Institute of Biomedicine, Gasan-dong, Geumcheon-gu, Seoul, Korea;

关键词: Allogeneic;    Chondrocyte;    Immunogenicity;    Immunomodulation;    PD-L1;    PD-L2;   

DOI  :  10.1186/s12891-017-1547-8

 received in 2016-06-23, accepted in 2017-05-04,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundInvossa™ (TissueGene-C) is a cell and gene therapy for osteoarthritis. It is composed of primary human chondrocytes (hChonJ cells) and irradiated human chondrocytes modified to express TGF-β1 (hChonJb#7 cells). The hChonJ cells were isolated from a polydactyly donor, and TGF-β1 cDNA was delivered to the cells, generating hChonJb#7 cells. Since the cells are allogeneic, the concern of immune response against cells has been raised. In this study, we investigated the immunogenicity of allogenic human chondrocyte, hChonJ cells.MethodsThe immunological properties of hChonJ cells were investigated through the analysis of surface marker expression and the effect on allogeneic T cell proliferation. Flow cytometry and RT-PCR analysis were performed to analyze the surface marker expression related to immune response, such as major histocompatibility complex (MHC) class I, class II, T cell co-stimulatory molecules and T cell co-inhibitory molecules. A mixed lymphocyte reaction (MLR) was conducted to evaluate how allogeneic T cells would respond to hChonJ cells.ResultsWe observed that hChonJ cells did not express MHC class II and T cell co-stimulatory molecules, but expressed T cell co-inhibitory molecule PD-L2. IFN-γ treatment induced the expression of PD-L1, and up-regulated the expression of PD-L2. Also, we observed that hChonJ cells did not stimulate T cell proliferation from a MHC-mismatched donor. Further, they could suppress the proliferation of activated T cells. We also observed that the blockade of PD-L1 and/or PD-L2 with specific neutralizing antibody could lead to the restoration of allo-reactive T cell proliferation.ConclusionsWe showed that hChonJ cells were not immunogenic but immunosuppressive, and that this phenomenon was mediated by co-inhibitory molecules PD-L1 and PD-L2 on hChonJ cells in a contact-dependent manner.

【 授权许可】

CC BY   
© The Author(s). 2017