PMID- 31356169
OWN - NLM
STAT- MEDLINE
DCOM- 20200225
LR  - 20200309
IS  - 2573-7732 (Electronic)
IS  - 2573-7732 (Linking)
VI  - 3
IP  - 6
DP  - 2019 Jun 26
TI  - Development and Characterization of a Preclinical Model for the Evaluation of 
      CD205-Mediated Antigen Delivery Therapeutics in Type 1 Diabetes.
PG  - 236-253
LID - 10.4049/immunohorizons.1900014 [doi]
AB  - Dendritic cells (DCs) are crucial for the production of adaptive immune responses 
      to disease-causing microbes. However, in the steady state (i.e., in the absence 
      of an infection or when Ags are experimentally delivered without a DC-activating 
      adjuvant), DCs present Ags to T cells in a tolerogenic manner and are important 
      for the establishment of peripheral tolerance. Delivery of islet Ags to DCs using 
      Ag-linked Abs to the DC endocytic receptor CD205 has shown promise in the NOD 
      mouse model of type 1 diabetes (T1D). It is important to note, however, that all 
      myeloid DCs express CD205 in humans, whereas in mice, only one of the classical 
      DC subsets does (classical DC1; CD8alpha(+) in spleen). Thus, the evaluation of 
      CD205-targeted treatments in mice will likely not accurately predict the results 
      observed in humans. To overcome this challenge, we have developed and 
      characterized a novel NOD mouse model in which all myeloid DCs transgenically 
      express human CD205 (hCD205). This NOD.hCD205 strain displays a similar T1D 
      incidence profile to standard NOD mice. The presence of the transgene does not 
      alter DC development, phenotype, or function. Importantly, the DCs are able to 
      process and present Ags delivered via hCD205. Because Ags taken up via hCD205 can 
      be presented on both class I and class II MHC, both CD4(+) and CD8(+) T cells can 
      be modulated. As both T cell subsets are important for T1D pathogenesis, 
      NOD.hCD205 mice represent a unique, patient-relevant tool for the development and 
      optimization of DC-directed T1D therapies.
CI  - Copyright (c) 2019 The Authors.
FAU - Schloss, Jennifer
AU  - Schloss J
AUID- ORCID: 0000-0001-6739-0902
AD  - Department of Microbiology and Immunology, Albert Einstein College of Medicine, 
      Bronx, NY 10461.
FAU - Ali, Riyasat
AU  - Ali R
AUID- ORCID: 0000-0003-4022-276X
AD  - Department of Microbiology and Immunology, Albert Einstein College of Medicine, 
      Bronx, NY 10461.
FAU - Babad, Jeffrey
AU  - Babad J
AUID- ORCID: 0000-0002-2586-1371
AD  - Department of Microbiology and Immunology, Albert Einstein College of Medicine, 
      Bronx, NY 10461.
FAU - Guerrero-Ros, Ignacio
AU  - Guerrero-Ros I
AUID- ORCID: 0000-0003-2294-9092
AD  - Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461.
FAU - Pongsachai, Jillamika
AU  - Pongsachai J
AD  - Department of Microbiology and Immunology, Albert Einstein College of Medicine, 
      Bronx, NY 10461.
FAU - He, Li-Zhen
AU  - He LZ
AUID- ORCID: 0000-0001-8206-761X
AD  - Celldex Therapeutics Inc., Hampton, NJ 08827.
FAU - Keler, Tibor
AU  - Keler T
AD  - Celldex Therapeutics Inc., Hampton, NJ 08827.
FAU - DiLorenzo, Teresa P
AU  - DiLorenzo TP
AUID- ORCID: 0000-0003-4337-3598
AD  - Department of Microbiology and Immunology, Albert Einstein College of Medicine, 
      Bronx, NY 10461; teresa.dilorenzo@einstein.yu.edu.
AD  - Division of Endocrinology, Department of Medicine, Albert Einstein College of 
      Medicine, Bronx, NY 10461.
AD  - Einstein-Mount Sinai Diabetes Research Center, Albert Einstein College of 
      Medicine, Bronx, NY 10461; and.
AD  - The Fleischer Institute for Diabetes and Metabolism, Albert Einstein College of 
      Medicine, Bronx, NY 10461.
LA  - eng
GR  - F30 DK103368/DK/NIDDK NIH HHS/United States
GR  - R01 DK064315/DK/NIDDK NIH HHS/United States
GR  - R01 DK120420/DK/NIDDK NIH HHS/United States
GR  - R03 AI119225/AI/NIAID NIH HHS/United States
GR  - P30 DK020541/DK/NIDDK NIH HHS/United States
GR  - R01 DK094327/DK/NIDDK NIH HHS/United States
GR  - R01 AI123730/AI/NIAID NIH HHS/United States
GR  - T32 GM007288/GM/NIGMS NIH HHS/United States
GR  - P30 CA013330/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20190626
PL  - United States
TA  - Immunohorizons
JT  - ImmunoHorizons
JID - 101708159
RN  - 0 (Antigens, CD)
RN  - 0 (DEC-205 receptor)
RN  - 0 (Lectins, C-Type)
RN  - 0 (Minor Histocompatibility Antigens)
RN  - 0 (Receptors, Cell Surface)
SB  - IM
MH  - Animals
MH  - Antigen Presentation
MH  - Antigens, CD/genetics/*metabolism
MH  - CD4-Positive T-Lymphocytes/*immunology
MH  - CD8-Positive T-Lymphocytes/*immunology
MH  - Cells, Cultured
MH  - Dendritic Cells/*immunology
MH  - Diabetes Mellitus, Type 1/*immunology
MH  - Disease Models, Animal
MH  - Drug Evaluation, Preclinical
MH  - Humans
MH  - Immune Tolerance
MH  - Immunotherapy/*methods
MH  - Lectins, C-Type/genetics/*metabolism
MH  - Lymphocyte Activation
MH  - Mice
MH  - Mice, Inbred NOD
MH  - Mice, Transgenic
MH  - Minor Histocompatibility Antigens/genetics/*metabolism
MH  - Receptors, Cell Surface/genetics/*metabolism
PMC - PMC6668927
MID - NIHMS1035707
EDAT- 2019/07/30 06:00
MHDA- 2020/02/26 06:00
PMCR- 2019/07/31
CRDT- 2019/07/30 06:00
PHST- 2019/03/04 00:00 [received]
PHST- 2019/06/07 00:00 [accepted]
PHST- 2019/07/30 06:00 [entrez]
PHST- 2019/07/30 06:00 [pubmed]
PHST- 2020/02/26 06:00 [medline]
PHST- 2019/07/31 00:00 [pmc-release]
AID - 3/6/236 [pii]
AID - 10.4049/immunohorizons.1900014 [doi]
PST - epublish
SO  - Immunohorizons. 2019 Jun 26;3(6):236-253. doi: 10.4049/immunohorizons.1900014.