PMID- 30858365
OWN - NLM
STAT- MEDLINE
DCOM- 20200529
LR  - 20220416
IS  - 2092-6413 (Electronic)
IS  - 1226-3613 (Print)
IS  - 1226-3613 (Linking)
VI  - 51
IP  - 3
DP  - 2019 Mar 11
TI  - Allogeneic ADSCs induce CD8 T cell-mediated cytotoxicity and faster cell death 
      after exposure to xenogeneic serum or proinflammatory cytokines.
PG  - 1-10
LID - 10.1038/s12276-019-0231-5 [doi]
LID - 28
AB  - This study examined the induction of recipient T-cell cytotoxicity after exposure 
      to allogeneic adipose-derived mesenchymal stem cells (ADSCs). ADSCs pre-exposed 
      to xenogeneic serum significantly induced cytotoxicity through CD8 T-cell 
      granzyme B secretion after allogeneic antigen stimulation, and this effect was 
      increased with prolonged reaction time. ADSCs pretreated with proinflammatory 
      cytokines also induced cytotoxicity through granzyme B secretion and 
      significantly increased human leukocyte antigen (HLA)-ABC expression. T-cell 
      cytotoxicity towards ADSCs grown in xeno-free medium (XF-ADSCs) was lower than 
      that towards ADSCs exposed to xenogeneic serum or proinflammatory cytokines, but 
      XF-ADSCs still induced cytotoxicity. We further investigated the causes of T-cell 
      cytotoxicity towards XF-ADSCs. XF-ADSC death was effectively inhibited by 
      HLA-blocking antibodies, suggesting that ADSC HLAs are a major cause of 
      alloreactive T-cell generation. These results indicated that culturing of 
      allogeneic ADSCs with recipient serum may alleviate alloreactive CD8 T-cell 
      cytotoxicity. Ultimately, development of therapeutic agents using autologous 
      ADSCs would be a suitable way to avoid immunogenicity and CD8 T cell-mediated 
      cytotoxicity, but more attention should be paid to the potential immunogenicity 
      of allogeneic ADSCs, which could perhaps be mitigated through the use of 
      immunosuppressants.
FAU - Chang, Sung-Ho
AU  - Chang SH
AD  - Institute of Endemic Diseases, Medical Research Center, Seoul National University 
      College of Medicine, Seoul, Republic of Korea.
AD  - Xenotransplantation Research Center, Seoul National University College of 
      Medicine, Seoul, Republic of Korea.
AD  - Department of Microbiology and Immunology, Seoul National University College of 
      Medicine, Seoul, Republic of Korea.
AD  - Department of Biochemistry and Molecular Biology, Asan Medical Center, University 
      of Ulsan College of Medicine, Seoul, Republic of Korea.
FAU - Park, Chung-Gyu
AU  - Park CG
AUID- ORCID: 0000-0003-4083-8791
AD  - Institute of Endemic Diseases, Medical Research Center, Seoul National University 
      College of Medicine, Seoul, Republic of Korea. chgpark@snu.ac.kr.
AD  - Xenotransplantation Research Center, Seoul National University College of 
      Medicine, Seoul, Republic of Korea. chgpark@snu.ac.kr.
AD  - Department of Microbiology and Immunology, Seoul National University College of 
      Medicine, Seoul, Republic of Korea. chgpark@snu.ac.kr.
AD  - Department of Biomedical Sciences, Seoul National University College of Medicine, 
      Seoul, Republic of Korea. chgpark@snu.ac.kr.
AD  - Cancer Research Institute, Seoul National University College of Medicine, Seoul, 
      Republic of Korea. chgpark@snu.ac.kr.
LA  - eng
GR  - 14172MFDS974/Ministry of Food and Drug Safety (MFDS)/International
GR  - 14172MFDS974/Ministry of Food and Drug Safety (MFDS)/International
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190311
PL  - United States
TA  - Exp Mol Med
JT  - Experimental & molecular medicine
JID - 9607880
RN  - 0 (Cytokines)
SB  - IM
MH  - Animals
MH  - CD8-Positive T-Lymphocytes/cytology/*immunology
MH  - Cattle
MH  - Cell Death
MH  - Cell Survival
MH  - Cells, Cultured
MH  - Cytokines/*immunology
MH  - Humans
MH  - Mesenchymal Stem Cells/cytology/*immunology
MH  - Serum/*immunology
PMC - PMC6412000
COIS- The authors declare that they have no conflict of interest.
EDAT- 2019/03/13 06:00
MHDA- 2020/05/30 06:00
PMCR- 2019/03/11
CRDT- 2019/03/13 06:00
PHST- 2018/02/13 00:00 [received]
PHST- 2018/10/29 00:00 [accepted]
PHST- 2018/09/02 00:00 [revised]
PHST- 2019/03/13 06:00 [entrez]
PHST- 2019/03/13 06:00 [pubmed]
PHST- 2020/05/30 06:00 [medline]
PHST- 2019/03/11 00:00 [pmc-release]
AID - 10.1038/s12276-019-0231-5 [pii]
AID - 231 [pii]
AID - 10.1038/s12276-019-0231-5 [doi]
PST - epublish
SO  - Exp Mol Med. 2019 Mar 11;51(3):1-10. doi: 10.1038/s12276-019-0231-5.