PMID- 23939944
OWN - NLM
STAT- MEDLINE
DCOM- 20141106
LR  - 20211021
IS  - 1549-4918 (Electronic)
IS  - 1066-5099 (Print)
IS  - 1066-5099 (Linking)
VI  - 32
IP  - 1
DP  - 2014 Jan
TI  - Generation of functional, antigen-specific CD8+ human T cells from cord blood 
      stem cells using exogenous Notch and tetramer-TCR signaling.
PG  - 93-104
LID - 10.1002/stem.1512 [doi]
AB  - In vitro differentiation of mouse and human stem cells into early T cells has 
      been successfully demonstrated using artificial Notch signaling systems. However, 
      generation of mature, antigen-specific, functional T cells, directly from human 
      stem cells has remained elusive, except when using stromal coculture of stem 
      cells retrovirally transfected with antigen-specific T cell receptors (TCRs). 
      Here we show that human umbilical cord blood (UCB)-derived CD34+CD38-/low 
      hematopoietic stem cells can be successfully differentiated into functional, 
      antigen-specific cytotoxic CD8+ T cells without direct stromal coculture or 
      retroviral TCR transfection. Surface-immobilized Notch ligands (DLL1) and stromal 
      cell conditioned medium successfully induced the development of CD1a+CD7+ and 
      CD4+CD8+ early T cells. These cells, upon continued culture with cytomegalovirus 
      (CMV) or influenza-A virus M1 (GIL) epitope-loaded human leukocyte antigen 
      (HLA)-A*0201 tetramers, resulted in the generation of a polyclonal population of 
      CMV-specific or GIL-specific CD8+ T cells, respectively. Upon further activation 
      with antigen-loaded target cells, these antigen-specific, stem cell-derived T 
      cells exhibited cytolytic functionality, specifically CD107a surface 
      mobilization, interferon gamma (IFNg) production, and Granzyme B secretion. Such 
      scalable, in vitro generation of functional, antigen-specific T cells from human 
      stem cells could eventually provide a readily available cell source for adoptive 
      transfer immunotherapies and also allow better understanding of human T cell 
      development.
CI  - Copyright (c) 2013 AlphaMed Press.
FAU - Fernandez, Irina
AU  - Fernandez I
AD  - Department of Biomedical Engineering, The University of Texas at Austin, Austin, 
      Texas, USA; Dell Pediatric Research Institute and, The University of Texas at 
      Austin, Austin, Texas, USA.
FAU - Ooi, Tracy P
AU  - Ooi TP
FAU - Roy, Krishnendu
AU  - Roy K
LA  - eng
GR  - R21 EB011666/EB/NIBIB NIH HHS/United States
GR  - R21 HL089843/HL/NHLBI NIH HHS/United States
GR  - HL089843/HL/NHLBI NIH HHS/United States
GR  - EB011666/EB/NIBIB NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - England
TA  - Stem Cells
JT  - Stem cells (Dayton, Ohio)
JID - 9304532
RN  - 0 (Culture Media)
RN  - 0 (HLA-A*02:01 antigen)
RN  - 0 (HLA-A2 Antigen)
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - 0 (Receptors, Notch)
SB  - IM
MH  - Animals
MH  - CD8-Positive T-Lymphocytes/*cytology/drug effects/immunology/metabolism
MH  - Cell Differentiation/drug effects
MH  - Cells, Cultured
MH  - Culture Media
MH  - Fetal Blood/*cytology/drug effects/immunology/metabolism
MH  - Flow Cytometry
MH  - HLA-A2 Antigen/immunology/pharmacology
MH  - Hematopoietic Stem Cells/*cytology/drug effects/immunology/metabolism
MH  - Humans
MH  - Mice
MH  - Receptors, Antigen, T-Cell/*metabolism
MH  - Receptors, Notch/*metabolism
MH  - Signal Transduction
PMC - PMC4193361
MID - NIHMS517502
OTO - NOTNLM
OT  - Adult hematopoietic stem cells
OT  - CD34+ cells
OT  - Cytotoxic T cells
OT  - Human cord blood
EDAT- 2013/08/14 06:00
MHDA- 2014/11/07 06:00
PMCR- 2015/01/01
CRDT- 2013/08/14 06:00
PHST- 2013/01/22 00:00 [received]
PHST- 2013/07/24 00:00 [accepted]
PHST- 2013/08/14 06:00 [entrez]
PHST- 2013/08/14 06:00 [pubmed]
PHST- 2014/11/07 06:00 [medline]
PHST- 2015/01/01 00:00 [pmc-release]
AID - 10.1002/stem.1512 [doi]
PST - ppublish
SO  - Stem Cells. 2014 Jan;32(1):93-104. doi: 10.1002/stem.1512.