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- Title
Immunogenicity and immunomodulatory effects of the human chondrocytes, hChonJ.
- Authors
Chae-Lyul Lim; Yeon-Ju Lee; Jong-Ho Cho; Heonsik Choi; Bumsup Lee; Myung Chul Lee; Sujeong Kim; Lim, Chae-Lyul; Lee, Yeon-Ju; Cho, Jong-Ho; Choi, Heonsik; Lee, Bumsup; Lee, Myung Chul; Kim, Sujeong
- Abstract
<bold>Background: </bold>Invossa™ (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.<bold>Methods: </bold>The 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.<bold>Results: </bold>We 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.<bold>Conclusions: </bold>We 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.
- Subjects
IMMUNOGENETICS; IMMUNOREGULATION; CARTILAGE cells; MAJOR histocompatibility complex; OSTEOARTHRITIS; IMMUNE system physiology; CELL culture; CELLULAR immunity; FLOW cytometry; IMMUNOLOGICAL tolerance; RESEARCH methodology; TISSUE culture
- Publication
BMC Musculoskeletal Disorders, 2017, Vol 18, p1
- ISSN
1471-2474
- Publication type
journal article
- DOI
10.1186/s12891-017-1547-8