Allogeneic ADSCs Induce the Production of Alloreactive Memory-CD8 T Cells through HLA-ABC Antigens
We investigated the immunogenicity of allogeneic human adipose-derived mesenchymal stem cells (ADSCs) through the production of alloreactive-CD8 T and -memory CD8 T cells, based on their human leukocyte antigen (HLA) expression. In surface antigen analysis, ADSCs do not express co-stimulatory molecu...
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| Format: | Article |
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MDPI AG
2020-05-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/9/5/1246 |
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| author | Sung-Ho Chang Hyun Je Kim Chung-Gyu Park |
| author_facet | Sung-Ho Chang Hyun Je Kim Chung-Gyu Park |
| author_sort | Sung-Ho Chang |
| collection | DOAJ |
| description | We investigated the immunogenicity of allogeneic human adipose-derived mesenchymal stem cells (ADSCs) through the production of alloreactive-CD8 T and -memory CD8 T cells, based on their human leukocyte antigen (HLA) expression. In surface antigen analysis, ADSCs do not express co-stimulatory molecules, but expresses HLA-ABC, which is further increased by exposure to the pro-inflammatory cytokines as well as IFN-γ alone. For immunogenicity analysis, allogeneic ADSCs cultured in xenofree medium (XF-ADSCs) were incubated with the recipient immune cells for allogeneic–antigen stimulation. As a result, XF-ADSCs induced IFN-γ and IL-17A release by alloreactive-CD8 T cells and the production of alloreactive-CD8 T cell through a direct pathway, although they have immunomodulatory activity. In the analysis of alloreactive memory CD8 T cells, XF-ADSCs also significantly induced the production of CFSE-low-CD8 TEM and -CD8 TCM cells. However, HLA-blocking antibodies significantly inhibited the production of CFSE-low memory-CD8 T cells, indicating that HLAs are the main antigens responsible for the development of allogeneic ADSCs’ immunogenicity. These results suggested that HLA surface antigens expressed in allogeneic MSCs should be solved in order to address concerns related to the immunogenicity problem. |
| first_indexed | 2024-03-10T19:45:41Z |
| format | Article |
| id | doaj.art-5d7fbbeb8c6640e28182bb556d118a2c |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T19:45:41Z |
| publishDate | 2020-05-01 |
| publisher | MDPI AG |
| record_format | Article |
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| spelling | doaj.art-5d7fbbeb8c6640e28182bb556d118a2c2023-11-20T00:50:41ZengMDPI AGCells2073-44092020-05-0195124610.3390/cells9051246Allogeneic ADSCs Induce the Production of Alloreactive Memory-CD8 T Cells through HLA-ABC AntigensSung-Ho Chang0Hyun Je Kim1Chung-Gyu Park2Departments of Oral Microbiology and Immunology, School of Dentistry and Dental Research Institute, Seoul National University, Seoul 03080, KoreaDepartment of Microbiology and Immunology, Seoul National University College of Medicine, Seoul 03080, KoreaDepartment of Microbiology and Immunology, Seoul National University College of Medicine, Seoul 03080, KoreaWe investigated the immunogenicity of allogeneic human adipose-derived mesenchymal stem cells (ADSCs) through the production of alloreactive-CD8 T and -memory CD8 T cells, based on their human leukocyte antigen (HLA) expression. In surface antigen analysis, ADSCs do not express co-stimulatory molecules, but expresses HLA-ABC, which is further increased by exposure to the pro-inflammatory cytokines as well as IFN-γ alone. For immunogenicity analysis, allogeneic ADSCs cultured in xenofree medium (XF-ADSCs) were incubated with the recipient immune cells for allogeneic–antigen stimulation. As a result, XF-ADSCs induced IFN-γ and IL-17A release by alloreactive-CD8 T cells and the production of alloreactive-CD8 T cell through a direct pathway, although they have immunomodulatory activity. In the analysis of alloreactive memory CD8 T cells, XF-ADSCs also significantly induced the production of CFSE-low-CD8 TEM and -CD8 TCM cells. However, HLA-blocking antibodies significantly inhibited the production of CFSE-low memory-CD8 T cells, indicating that HLAs are the main antigens responsible for the development of allogeneic ADSCs’ immunogenicity. These results suggested that HLA surface antigens expressed in allogeneic MSCs should be solved in order to address concerns related to the immunogenicity problem.https://www.mdpi.com/2073-4409/9/5/1246adipose-derived mesenchymal stem cells (ADSCs)direct pathwayalloreactive memory CD8 T cellshuman leukocyte antigen (HLA)immunogenicity |
| spellingShingle | Sung-Ho Chang Hyun Je Kim Chung-Gyu Park Allogeneic ADSCs Induce the Production of Alloreactive Memory-CD8 T Cells through HLA-ABC Antigens Cells adipose-derived mesenchymal stem cells (ADSCs) direct pathway alloreactive memory CD8 T cells human leukocyte antigen (HLA) immunogenicity |
| title | Allogeneic ADSCs Induce the Production of Alloreactive Memory-CD8 T Cells through HLA-ABC Antigens |
| title_full | Allogeneic ADSCs Induce the Production of Alloreactive Memory-CD8 T Cells through HLA-ABC Antigens |
| title_fullStr | Allogeneic ADSCs Induce the Production of Alloreactive Memory-CD8 T Cells through HLA-ABC Antigens |
| title_full_unstemmed | Allogeneic ADSCs Induce the Production of Alloreactive Memory-CD8 T Cells through HLA-ABC Antigens |
| title_short | Allogeneic ADSCs Induce the Production of Alloreactive Memory-CD8 T Cells through HLA-ABC Antigens |
| title_sort | allogeneic adscs induce the production of alloreactive memory cd8 t cells through hla abc antigens |
| topic | adipose-derived mesenchymal stem cells (ADSCs) direct pathway alloreactive memory CD8 T cells human leukocyte antigen (HLA) immunogenicity |
| url | https://www.mdpi.com/2073-4409/9/5/1246 |
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