PMID- 25744551
OWN - NLM
STAT- MEDLINE
DCOM- 20160617
LR  - 20181113
IS  - 1440-1711 (Electronic)
IS  - 0818-9641 (Print)
IS  - 0818-9641 (Linking)
VI  - 93
IP  - 8
DP  - 2015 Sep
TI  - Conserved and divergent aspects of human T-cell development and migration in 
      humanized mice.
PG  - 716-26
LID - 10.1038/icb.2015.38 [doi]
AB  - Humanized mice represent an important model to study the development and function 
      of the human immune system. While it is known that mouse thymic stromal cells can 
      support human T-cell development, the extent of interspecies cross-talk and the 
      degree to which these systems recapitulate normal human T-cell development remain 
      unclear. To address these questions, we compared conventional and 
      non-conventional T-cell development in a neonatal chimera humanized mouse model 
      with that seen in human fetal and neonatal thymus samples, and also examined the 
      impact of a human HLA-A2 transgene expressed by the mouse stroma. Given that 
      dynamic migration and cell-cell interactions are essential for T-cell 
      differentiation, we also studied the intrathymic migration pattern of human 
      thymocytes developing in a murine thymic environment. We found that both 
      conventional T-cell development and intra-thymic migration patterns in humanized 
      mice closely resemble human thymopoiesis. Additionally, we show that developing 
      human thymocytes engage in short, serial interactions with other human 
      hematopoietic-derived cells. However, non-conventional T-cell differentiation in 
      humanized mice differed from both fetal and neonatal human thymopoiesis, 
      including a marked deficiency of Foxp3(+) T-cell development. These data suggest 
      that although the murine thymic microenvironment can support a number of aspects 
      of human T-cell development, important differences remain, and additional 
      human-specific factors may be required.
FAU - Halkias, Joanna
AU  - Halkias J
AD  - Division of Immunology and Pathogenesis, Department of Molecular and Cell 
      Biology, UC Berkeley, Berkeley, CA, USA.
AD  - Division of Neonatology, Department of Pediatrics, UCSF Benioff Children's 
      Hospital Oakland, Oakland, CA, USA.
FAU - Yen, Bonnie
AU  - Yen B
AD  - Division of Immunology and Pathogenesis, Department of Molecular and Cell 
      Biology, UC Berkeley, Berkeley, CA, USA.
FAU - Taylor, Kayleigh T
AU  - Taylor KT
AD  - Division of Immunology and Pathogenesis, Department of Molecular and Cell 
      Biology, UC Berkeley, Berkeley, CA, USA.
FAU - Reinhartz, Olaf
AU  - Reinhartz O
AD  - Division of Cardiothoracic Surgery, Department of Pediatrics, UCSF Benioff 
      Children's Hospital Oakland, Oakland, CA, USA.
AD  - Division of Pediatric Cardiac Surgery, Department of Cardiothoracic Surgery, 
      Lucile Packard Children's Hospital/Stanford University, Palo Alto, CA, USA.
FAU - Winoto, Astar
AU  - Winoto A
AD  - Division of Immunology and Pathogenesis, Department of Molecular and Cell 
      Biology, UC Berkeley, Berkeley, CA, USA.
FAU - Robey, Ellen A
AU  - Robey EA
AD  - Division of Immunology and Pathogenesis, Department of Molecular and Cell 
      Biology, UC Berkeley, Berkeley, CA, USA.
FAU - Melichar, Heather J
AU  - Melichar HJ
AD  - Division of Immunology and Pathogenesis, Department of Molecular and Cell 
      Biology, UC Berkeley, Berkeley, CA, USA.
LA  - eng
GR  - R01 AI064227/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150306
PL  - United States
TA  - Immunol Cell Biol
JT  - Immunology and cell biology
JID - 8706300
RN  - 0 (Biomarkers)
RN  - 0 (HLA-A2 Antigen)
SB  - IM
MH  - Animals
MH  - Biomarkers
MH  - Cell Communication
MH  - *Cell Differentiation
MH  - *Cell Movement
MH  - Cellular Microenvironment
MH  - Gene Expression
MH  - Genes, Reporter
MH  - HLA-A2 Antigen/genetics/immunology/metabolism
MH  - Humans
MH  - Immune System/cytology/physiology
MH  - Lymphopoiesis
MH  - Mice
MH  - Mice, Transgenic
MH  - Models, Animal
MH  - Organogenesis
MH  - Phenotype
MH  - T-Lymphocyte Subsets/cytology/physiology
MH  - T-Lymphocytes/*cytology/*physiology
MH  - Thymocytes/cytology/physiology
MH  - Thymus Gland/cytology/embryology/physiology
PMC - PMC4575952
EDAT- 2015/03/07 06:00
MHDA- 2016/06/18 06:00
PMCR- 2015/09/21
CRDT- 2015/03/07 06:00
PHST- 2014/10/06 00:00 [received]
PHST- 2015/02/09 00:00 [revised]
PHST- 2015/02/09 00:00 [accepted]
PHST- 2015/03/07 06:00 [entrez]
PHST- 2015/03/07 06:00 [pubmed]
PHST- 2016/06/18 06:00 [medline]
PHST- 2015/09/21 00:00 [pmc-release]
AID - icb201538 [pii]
AID - 10.1038/icb.2015.38 [doi]
PST - ppublish
SO  - Immunol Cell Biol. 2015 Sep;93(8):716-26. doi: 10.1038/icb.2015.38. Epub 2015 Mar 
      6.