PMID- 32578199
OWN - NLM
STAT- MEDLINE
DCOM- 20210119
LR  - 20211102
IS  - 1365-2249 (Electronic)
IS  - 0009-9104 (Print)
IS  - 0009-9104 (Linking)
VI  - 202
IP  - 2
DP  - 2020 Nov
TI  - The suppressive effect on CD4 T cell alloresponse against endothelial HLA-DR via 
      PD-L1 induced by anti-A/B ligation.
PG  - 249-261
LID - 10.1111/cei.13482 [doi]
AB  - While donor-specific human leukocyte antigen (HLA) antibodies are a frequent 
      cause for chronic antibody-mediated rejection in organ transplantation, this is 
      not the case for antibodies targeting blood group antigens, as ABO-incompatible 
      (ABO-I) organ transplantation has been associated with a favorable graft outcome. 
      Here, we explored the role of CD4 T cell-mediated alloresponses against 
      endothelial HLA-D-related (DR) in the presence of anti-HLA class I or anti-A/B 
      antibodies. CD4 T cells, notably CD45RA-memory CD4 T cells, undergo extensive 
      proliferation in response to endothelial HLA-DR. The CD4 T cell proliferative 
      response was enhanced in the presence of anti-HLA class I, but attenuated in the 
      presence of anti-A/B antibodies. Microarray analysis and molecular profiling 
      demonstrated that the expression of CD274 programmed cell death ligand 1 (PD-L1) 
      increased in response to anti-A/B ligation-mediated extracellular 
      signal-regulated kinase (ERK) inactivation in endothelial cells that were 
      detected even in the presence of interferon-gamma stimulation. Anti-PD-1 antibody 
      enhanced CD4 T cell proliferation, and blocked the suppressive effect of the 
      anti-A/B antibodies. Educated CD25(+) CD127(-) regulatory T cells (edu.T(regs) ) 
      were more effective at preventing CD4 T cell alloresponses to endothelial cells 
      compared with naive T(reg) ; anti-A/B antibodies were not involved in the T(reg) 
      -mediated events. Finally, amplified expression of transcript encoding PD-L1 was 
      observed in biopsy samples from ABO-I renal transplants when compared with those 
      from ABO-identical/compatible transplants. Taken together, our findings 
      identified a possible factor that might prevent graft rejection and thus 
      contribute to a favorable outcome in ABO-I renal transplantation.
CI  - (c) 2020 British Society for Immunology.
FAU - Iwasaki, K
AU  - Iwasaki K
AUID- ORCID: 0000-0003-3229-5192
AD  - Department of Kidney Disease and Transplant Immunology, Aichi Medical University 
      School of Medicine, Nagakute, Japan.
FAU - Hamana, H
AU  - Hamana H
AD  - Department of Immunology, Graduate School of Medicine and Pharmaceutical 
      Sciences, University of Toyama, Toyama, Japan.
FAU - Kishi, H
AU  - Kishi H
AD  - Department of Immunology, Graduate School of Medicine and Pharmaceutical 
      Sciences, University of Toyama, Toyama, Japan.
FAU - Yamamoto, T
AU  - Yamamoto T
AD  - Department of Transplant Surgery, Nagoya Daini Red Cross Hospital, Nagoya, Japan.
FAU - Hiramitsu, T
AU  - Hiramitsu T
AD  - Department of Transplant Surgery, Nagoya Daini Red Cross Hospital, Nagoya, Japan.
FAU - Okad, M
AU  - Okad M
AD  - Department of Transplant Surgery, Nagoya Daini Red Cross Hospital, Nagoya, Japan.
FAU - Tomosugi, T
AU  - Tomosugi T
AD  - Department of Transplant Surgery, Nagoya Daini Red Cross Hospital, Nagoya, Japan.
FAU - Takeda, A
AU  - Takeda A
AD  - Department of Transplant Surgery, Nagoya Daini Red Cross Hospital, Nagoya, Japan.
FAU - Narumi, S
AU  - Narumi S
AD  - Department of Transplant Surgery, Nagoya Daini Red Cross Hospital, Nagoya, Japan.
FAU - Watarai, Y
AU  - Watarai Y
AD  - Department of Transplant Surgery, Nagoya Daini Red Cross Hospital, Nagoya, Japan.
FAU - Miwa, Y
AU  - Miwa Y
AD  - Department of Kidney Disease and Transplant Immunology, Aichi Medical University 
      School of Medicine, Nagakute, Japan.
FAU - Okumura, M
AU  - Okumura M
AD  - Department of Renal Transplant Surgery, Aichi Medical University School of 
      Medicine, Nagakute, Aichi, Japan.
FAU - Matsuoka, Y
AU  - Matsuoka Y
AD  - Department of Renal Transplant Surgery, Aichi Medical University School of 
      Medicine, Nagakute, Aichi, Japan.
FAU - Horimi, K
AU  - Horimi K
AD  - Department of Renal Transplant Surgery, Aichi Medical University School of 
      Medicine, Nagakute, Aichi, Japan.
FAU - Muraguchi, A
AU  - Muraguchi A
AD  - Department of Immunology, Graduate School of Medicine and Pharmaceutical 
      Sciences, University of Toyama, Toyama, Japan.
FAU - Kobayash, T
AU  - Kobayash T
AD  - Department of Renal Transplant Surgery, Aichi Medical University School of 
      Medicine, Nagakute, Aichi, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200718
PL  - England
TA  - Clin Exp Immunol
JT  - Clinical and experimental immunology
JID - 0057202
RN  - 0 (ABO Blood-Group System)
RN  - 0 (B7-H1 Antigen)
RN  - 0 (CD274 protein, human)
RN  - 0 (HLA-DR Antigens)
RN  - 0 (Isoantibodies)
SB  - IM
MH  - ABO Blood-Group System/*immunology
MH  - B7-H1 Antigen/*immunology
MH  - Endothelial Cells/*immunology/pathology
MH  - Graft Rejection/immunology/pathology
MH  - HLA-DR Antigens/*immunology
MH  - Humans
MH  - Isoantibodies/*immunology
MH  - *Organ Transplantation
MH  - T-Lymphocytes, Regulatory/*immunology/pathology
PMC - PMC7597605
OTO - NOTNLM
OT  - PD-L1
OT  - T cell receptor
OT  - accommodation
OT  - alloresponse
OT  - antibody-mediated rejection
OT  - kidney transplantation
COIS- The authors have no financial conflicts of interest.
EDAT- 2020/06/25 06:00
MHDA- 2021/01/20 06:00
PMCR- 2021/11/01
CRDT- 2020/06/25 06:00
PHST- 2020/04/15 00:00 [received]
PHST- 2020/05/27 00:00 [revised]
PHST- 2020/06/15 00:00 [accepted]
PHST- 2020/06/25 06:00 [pubmed]
PHST- 2021/01/20 06:00 [medline]
PHST- 2020/06/25 06:00 [entrez]
PHST- 2021/11/01 00:00 [pmc-release]
AID - CEI13482 [pii]
AID - 10.1111/cei.13482 [doi]
PST - ppublish
SO  - Clin Exp Immunol. 2020 Nov;202(2):249-261. doi: 10.1111/cei.13482. Epub 2020 Jul 
      18.