PMID- 38446892
OWN - NLM
STAT- MEDLINE
DCOM- 20240308
LR  - 20240318
IS  - 2375-2548 (Electronic)
IS  - 2375-2548 (Linking)
VI  - 10
IP  - 10
DP  - 2024 Mar 8
TI  - Coxsackievirus infection induces direct pancreatic beta cell killing but poor 
      antiviral CD8(+) T cell responses.
PG  - eadl1122
LID - 10.1126/sciadv.adl1122 [doi]
LID - eadl1122
AB  - Coxsackievirus B (CVB) infection of pancreatic beta cells is associated with beta cell 
      autoimmunity and type 1 diabetes. We investigated how CVB affects human beta cells 
      and anti-CVB T cell responses. beta cells were efficiently infected by CVB in vitro, 
      down-regulated human leukocyte antigen (HLA) class I, and presented few, selected 
      HLA-bound viral peptides. Circulating CD8(+) T cells from CVB-seropositive 
      individuals recognized a fraction of these peptides; only another subfraction was 
      targeted by effector/memory T cells that expressed exhaustion marker PD-1. T 
      cells recognizing a CVB epitope cross-reacted with beta cell antigen GAD. Infected beta 
      cells, which formed filopodia to propagate infection, were more efficiently 
      killed by CVB than by CVB-reactive T cells. Our in vitro and ex vivo data 
      highlight limited CD8(+) T cell responses to CVB, supporting the rationale for 
      CVB vaccination trials for type 1 diabetes prevention. CD8(+) T cells recognizing 
      structural and nonstructural CVB epitopes provide biomarkers to differentially 
      follow response to infection and vaccination.
FAU - Vecchio, Federica
AU  - Vecchio F
AUID- ORCID: 0000-0003-4607-8818
AD  - Universite Paris Cite, Institut Cochin, CNRS, INSERM, Paris, France.
FAU - Carre, Alexia
AU  - Carre A
AUID- ORCID: 0000-0001-8144-7194
AD  - Universite Paris Cite, Institut Cochin, CNRS, INSERM, Paris, France.
FAU - Korenkov, Daniil
AU  - Korenkov D
AUID- ORCID: 0000-0001-8321-778X
AD  - Universite Paris Cite, Institut Cochin, CNRS, INSERM, Paris, France.
FAU - Zhou, Zhicheng
AU  - Zhou Z
AUID- ORCID: 0000-0001-9137-7951
AD  - Universite Paris Cite, Institut Cochin, CNRS, INSERM, Paris, France.
FAU - Apaolaza, Paola
AU  - Apaolaza P
AUID- ORCID: 0000-0002-7550-054X
AD  - Institute of Diabetes Research, Helmholtz Zentrum Munchen, German Research Center 
      for Environmental Health, Munich-Neuherberg, Germany.
AD  - German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany.
FAU - Tuomela, Soile
AU  - Tuomela S
AD  - Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska 
      Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
FAU - Burgos-Morales, Orlando
AU  - Burgos-Morales O
AD  - Universite Paris Cite, Institut Cochin, CNRS, INSERM, Paris, France.
FAU - Snowhite, Isaac
AU  - Snowhite I
AUID- ORCID: 0009-0008-9387-0318
AD  - Diabetes Research Institute, Leonard Miller School of Medicine, University of 
      Miami, Miami, FL, USA.
AD  - Department of Diabetes Immunology, Arthur Riggs Diabetes and Metabolism Research 
      Institute, Beckman Research Institute, City of Hope, Duarte, CA, USA.
FAU - Perez-Hernandez, Javier
AU  - Perez-Hernandez J
AUID- ORCID: 0000-0001-9712-2917
AD  - Universite Paris Cite, Institut Cochin, CNRS, INSERM, Paris, France.
FAU - Brandao, Barbara
AU  - Brandao B
AUID- ORCID: 0009-0008-0128-0100
AD  - Universite Paris Cite, Institut Cochin, CNRS, INSERM, Paris, France.
FAU - Afonso, Georgia
AU  - Afonso G
AUID- ORCID: 0000-0003-3759-7317
AD  - Universite Paris Cite, Institut Cochin, CNRS, INSERM, Paris, France.
FAU - Halliez, Clementine
AU  - Halliez C
AUID- ORCID: 0000-0002-5683-515X
AD  - Universite Paris Cite, Institut Cochin, CNRS, INSERM, Paris, France.
AD  - Assistance Publique Hopitaux de Paris, Service de Diabetologie et Immunologie 
      Clinique, Cochin Hospital, Paris, France.
FAU - Kaddis, John
AU  - Kaddis J
AUID- ORCID: 0000-0002-6752-7670
AD  - Department of Diabetes Immunology, Arthur Riggs Diabetes and Metabolism Research 
      Institute, Beckman Research Institute, City of Hope, Duarte, CA, USA.
AD  - Department of Diabetes and Cancer Discovery Science, Arthur Riggs Diabetes and 
      Metabolism Research Institute, Beckman Research Institute, City of Hope, Duarte, 
      CA, USA.
FAU - Kent, Sally C
AU  - Kent SC
AD  - Diabetes Center of Excellence, Department of Medicine, University of 
      Massachusetts Medical Chan School, Worcester, MA, USA.
FAU - Nakayama, Maki
AU  - Nakayama M
AUID- ORCID: 0000-0002-0009-3687
AD  - Barbara Davis Center for Diabetes, University of Colorado School of Medicine, 
      Aurora, CO, USA.
FAU - Richardson, Sarah J
AU  - Richardson SJ
AUID- ORCID: 0000-0002-1160-6062
AD  - Islet Biology Exeter (IBEx), Exeter Centre of Excellence for Diabetes Research 
      (EXCEED), Department of Clinical and Biomedical Sciences, University of Exeter 
      Medical School, Exeter, UK.
FAU - Vinh, Joelle
AU  - Vinh J
AUID- ORCID: 0000-0001-7184-2668
AD  - ESPCI Paris, PSL University, Spectrometrie de Masse Biologique et Proteomique, 
      CNRS UMR8249, Paris, France.
FAU - Verdier, Yann
AU  - Verdier Y
AUID- ORCID: 0000-0002-3319-0053
AD  - ESPCI Paris, PSL University, Spectrometrie de Masse Biologique et Proteomique, 
      CNRS UMR8249, Paris, France.
FAU - Laiho, Jutta
AU  - Laiho J
AUID- ORCID: 0000-0002-5443-4651
AD  - Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
FAU - Scharfmann, Raphael
AU  - Scharfmann R
AD  - Universite Paris Cite, Institut Cochin, CNRS, INSERM, Paris, France.
FAU - Solimena, Michele
AU  - Solimena M
AD  - German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany.
AD  - Paul Langerhans Institute Dresden (PLID), Helmholtz Munich, University Hospital 
      and Faculty of Medicine, TU Dresden, Dresden, Germany.
FAU - Marinicova, Zuzana
AU  - Marinicova Z
AUID- ORCID: 0009-0008-6416-8247
AD  - German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany.
AD  - Paul Langerhans Institute Dresden (PLID), Helmholtz Munich, University Hospital 
      and Faculty of Medicine, TU Dresden, Dresden, Germany.
FAU - Bismuth, Elise
AU  - Bismuth E
AD  - Assistance Publique Hopitaux de Paris, Service d'Endocrinologie Pediatrique, 
      Robert Debre Hospital, Paris, France.
FAU - Lucidarme, Nadine
AU  - Lucidarme N
AD  - Assistance Publique Hopitaux de Paris, Service de Pediatrie, Jean Verdier 
      Hospital, Bondy, France.
FAU - Sanchez, Janine
AU  - Sanchez J
AUID- ORCID: 0000-0003-3790-6140
AD  - Department of Pediatrics, Division of Pediatric Endocrinology, Leonard Miller 
      School of Medicine, University of Miami, Miami, FL, USA.
FAU - Bustamante, Carmen
AU  - Bustamante C
AD  - Department of Pediatrics, Division of Pediatric Endocrinology, Leonard Miller 
      School of Medicine, University of Miami, Miami, FL, USA.
FAU - Gomez, Patricia
AU  - Gomez P
AUID- ORCID: 0000-0002-3211-7647
AD  - Department of Pediatrics, Division of Pediatric Endocrinology, Leonard Miller 
      School of Medicine, University of Miami, Miami, FL, USA.
FAU - Buus, Soren
AU  - Buus S
AUID- ORCID: 0000-0001-8363-1999
AD  - Department of Immunology and Microbiology, Faculty of Health Sciences, University 
      of Copenhagen, Copenhagen, Denmark.
CN  - nPOD-Virus Working Group
FAU - You, Sylvaine
AU  - You S
AUID- ORCID: 0000-0002-1578-5205
AD  - Universite Paris Cite, Institut Cochin, CNRS, INSERM, Paris, France.
AD  - Indiana Biosciences Research Institute, Indianapolis, IN, USA.
FAU - Pugliese, Alberto
AU  - Pugliese A
AUID- ORCID: 0000-0002-7211-0319
AD  - Diabetes Research Institute, Leonard Miller School of Medicine, University of 
      Miami, Miami, FL, USA.
AD  - Department of Diabetes Immunology, Arthur Riggs Diabetes and Metabolism Research 
      Institute, Beckman Research Institute, City of Hope, Duarte, CA, USA.
FAU - Hyoty, Heikki
AU  - Hyoty H
AUID- ORCID: 0000-0003-0370-4145
AD  - Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
AD  - Fimlab Laboratories, Tampere, Finland.
AD  - Department of Pediatrics, Tampere University Hospital, Tampere, Finland.
FAU - Rodriguez-Calvo, Teresa
AU  - Rodriguez-Calvo T
AUID- ORCID: 0000-0003-1531-8583
AD  - Institute of Diabetes Research, Helmholtz Zentrum Munchen, German Research Center 
      for Environmental Health, Munich-Neuherberg, Germany.
AD  - German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany.
FAU - Flodstrom-Tullberg, Malin
AU  - Flodstrom-Tullberg M
AUID- ORCID: 0000-0003-2685-2052
AD  - Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska 
      Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
FAU - Mallone, Roberto
AU  - Mallone R
AUID- ORCID: 0000-0002-9846-8861
AD  - Universite Paris Cite, Institut Cochin, CNRS, INSERM, Paris, France.
AD  - Assistance Publique Hopitaux de Paris, Service de Diabetologie et Immunologie 
      Clinique, Cochin Hospital, Paris, France.
AD  - Indiana Biosciences Research Institute, Indianapolis, IN, USA.
LA  - eng
GR  - R01 DK099317/DK/NIDDK NIH HHS/United States
PT  - Journal Article
DEP - 20240306
PL  - United States
TA  - Sci Adv
JT  - Science advances
JID - 101653440
RN  - 0 (Antibodies)
RN  - 0 (Epitopes)
RN  - 0 (Peptides)
RN  - 0 (Antiviral Agents)
SB  - IM
UOF - bioRxiv. 2023 Aug 21;:. PMID: 37662376
MH  - Humans
MH  - CD8-Positive T-Lymphocytes
MH  - *Diabetes Mellitus, Type 1
MH  - *Insulin-Secreting Cells
MH  - Antibodies
MH  - *Coxsackievirus Infections
MH  - Epitopes
MH  - Peptides
MH  - Antiviral Agents
PMC - PMC10917340
EDAT- 2024/03/06 18:42
MHDA- 2024/03/08 06:43
PMCR- 2024/03/06
CRDT- 2024/03/06 14:04
PHST- 2024/03/08 06:43 [medline]
PHST- 2024/03/06 18:42 [pubmed]
PHST- 2024/03/06 14:04 [entrez]
PHST- 2024/03/06 00:00 [pmc-release]
AID - adl1122 [pii]
AID - 10.1126/sciadv.adl1122 [doi]
PST - ppublish
SO  - Sci Adv. 2024 Mar 8;10(10):eadl1122. doi: 10.1126/sciadv.adl1122. Epub 2024 Mar 
      6.