PMID- 37051254
OWN - NLM
STAT- MEDLINE
DCOM- 20230417
LR  - 20230417
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 14
DP  - 2023
TI  - Impaired tolerance to the autoantigen LL-37 in acute coronary syndrome.
PG  - 1113904
LID - 10.3389/fimmu.2023.1113904 [doi]
LID - 1113904
AB  - BACKGROUND: LL-37 is the only member of the cathelicidin family of antimicrobial 
      peptides in humans and is an autoantigen in several autoimmune diseases and in 
      acute coronary syndrome (ACS). In this report, we profiled the specific T cell 
      response to the autoimmune self-antigen LL-37 and investigated the factors 
      modulating the response in peripheral blood mononuclear cells (PBMCs) of healthy 
      subjects and ACS patients. METHODS AND RESULTS: The activation induced marker 
      (AIM) assay demonstrated differential T cell profiles characterized by the 
      persistence of CD134 and CD137, markers that impair tolerance and promote immune 
      effector and memory response, in ACS compared to Controls. Specifically, 
      CD8+CD69+CD137+ T cells were significantly increased by LL-37 stimulation in ACS 
      PBMCs. T effector cell response to LL-37 were either HLA dependent or independent 
      as determined by blocking with monoclonal antibody to either Class-I HLA or 
      Class-II HLA. Blocking of immune checkpoints PD-1 and CTLA-4 demonstrated the 
      control of self-reactive T cell response to LL-37 was modulated predominantly by 
      CTLA-4. Platelets from healthy controls down-modulated CD8+CD69+CD137+ T cell 
      response to LL-37 in autologous PBMCs. CD8+CD69+CD137+ T cell AIM profile 
      negatively correlated with platelet count in ACS patients. CONCLUSIONS: Our 
      report demonstrates that the immune response to the autoantigen LL-37 in ACS 
      patients is characterized specifically by CD8+CD69+CD137+ T cell AIM profile with 
      persistent T cell activation and the generation of immunologic memory. The 
      results provide potentially novel insight into mechanistic pathways of 
      antigen-specific immune signaling in ACS.
CI  - Copyright (c) 2023 Chernomordik, Cercek, Zhou, Zhao, Lio, Chyu, Shah and Dimayuga.
FAU - Chernomordik, Fernando
AU  - Chernomordik F
AD  - Oppenheimer Atherosclerosis Research Center, Department of Cardiology, Smidt 
      Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, United States.
FAU - Cercek, Bojan
AU  - Cercek B
AD  - Oppenheimer Atherosclerosis Research Center, Department of Cardiology, Smidt 
      Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, United States.
FAU - Zhou, Jianchang
AU  - Zhou J
AD  - Oppenheimer Atherosclerosis Research Center, Department of Cardiology, Smidt 
      Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, United States.
FAU - Zhao, Xiaoning
AU  - Zhao X
AD  - Oppenheimer Atherosclerosis Research Center, Department of Cardiology, Smidt 
      Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, United States.
FAU - Lio, Nicole Wai Man
AU  - Lio NWM
AD  - Oppenheimer Atherosclerosis Research Center, Department of Cardiology, Smidt 
      Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, United States.
FAU - Chyu, Kuang-Yuh
AU  - Chyu KY
AD  - Oppenheimer Atherosclerosis Research Center, Department of Cardiology, Smidt 
      Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, United States.
FAU - Shah, Prediman K
AU  - Shah PK
AD  - Oppenheimer Atherosclerosis Research Center, Department of Cardiology, Smidt 
      Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, United States.
FAU - Dimayuga, Paul C
AU  - Dimayuga PC
AD  - Oppenheimer Atherosclerosis Research Center, Department of Cardiology, Smidt 
      Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, United States.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230327
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Autoantigens)
RN  - 0 (CTLA-4 Antigen)
RN  - 0 (CAMP protein, human)
SB  - IM
MH  - Humans
MH  - *Acute Coronary Syndrome/metabolism
MH  - Autoantigens/metabolism
MH  - CD8-Positive T-Lymphocytes
MH  - CTLA-4 Antigen/metabolism
MH  - Leukocytes, Mononuclear
PMC - PMC10083408
OTO - NOTNLM
OT  - LL-37
OT  - T cells
OT  - acute coronary syndrome
OT  - immune checkpoint
OT  - platelets
OT  - self-antigen
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2023/04/14 06:00
MHDA- 2023/04/14 06:42
PMCR- 2023/03/27
CRDT- 2023/04/13 01:59
PHST- 2022/12/01 00:00 [received]
PHST- 2023/03/15 00:00 [accepted]
PHST- 2023/04/14 06:42 [medline]
PHST- 2023/04/13 01:59 [entrez]
PHST- 2023/04/14 06:00 [pubmed]
PHST- 2023/03/27 00:00 [pmc-release]
AID - 10.3389/fimmu.2023.1113904 [doi]
PST - epublish
SO  - Front Immunol. 2023 Mar 27;14:1113904. doi: 10.3389/fimmu.2023.1113904. 
      eCollection 2023.