PMID- 24120693
OWN - NLM
STAT- MEDLINE
DCOM- 20140210
LR  - 20131216
IS  - 1873-2399 (Electronic)
IS  - 0301-472X (Linking)
VI  - 42
IP  - 1
DP  - 2014 Jan
TI  - Human CD8+ memory and EBV-specific T cells show low alloreactivity in vitro and 
      in CD34+ stem cell-engrafted NOD/SCID/IL-2Rgammac null mice.
PG  - 28-38.e1-2
LID - S0301-472X(13)00753-4 [pii]
LID - 10.1016/j.exphem.2013.09.013 [doi]
AB  - Current strategies in cellular immunotherapy of cancer and viral infections 
      include the adoptive transfer of T cell receptor (TCR) and chimeric antigen 
      receptor engineered T cells. When using transient RNA expression systems in 
      clinical studies, multiple infusions with receptor-redirected T cells appear 
      necessary. However, in allogeneic hematopoietic stem-cell transplantation, 
      repeated transfer of donor-derived T cells increases the risk of alloreactive 
      graft-versus-host disease. We investigated naive-derived (TN), memory-derived 
      (TM), and Epstein Barr virus-specific (TEBV) CD8(+) T cell subsets for 
      alloreactivity upon redirection with RNA encoding a cytomegalovirus-specific 
      model TCR. We observed that alloreactivity to human leukocyte antigen 
      (HLA)-mismatched hematopoietic cells developed at much stronger levels in TN 
      compared with TM or TEBV populations in cytokine-release and cytotoxicity assays. 
      Cytomegalovirus-specific effector function was higher in TCR-transfected TEBV and 
      TM over TN cells. To measure alloreactivity in vivo, we reconstituted 
      NOD/SCID/IL-2Rgammac(null) mice with human CD34(+) stem cells and adoptively 
      transferred them with CD8(+) T cell subsets previously stimulated against cells 
      of the HLA-mismatched stem-cell donor. TN cells showed a significant ability to 
      eliminate CD34-derived hematopoietic cells, which was not found with TM and TEBV 
      cells. This reduced alloreactive potential along with strong effector function 
      upon receptor RNA engineering makes CD8(+) memory and EBV-specific T cells 
      advantageous tools in adoptive immunotherapy after allogeneic transplantation.
CI  - Copyright (c) 2014 ISEH - Society for Hematology and Stem Cells. Published by 
      Elsevier Inc. All rights reserved.
FAU - Thomas, Simone
AU  - Thomas S
AD  - Department of Medicine III, Hematology, Internal Oncology and Pneumology, 
      University Medical Center of Johannes Gutenberg University, Mainz, Germany. 
      Electronic address: simone.thomas@ukr.de.
FAU - Klobuch, Sebastian
AU  - Klobuch S
AD  - Department of Medicine III, Hematology, Internal Oncology and Pneumology, 
      University Medical Center of Johannes Gutenberg University, Mainz, Germany.
FAU - Sommer, Maria
AU  - Sommer M
AD  - Department of Medicine III, Hematology, Internal Oncology and Pneumology, 
      University Medical Center of Johannes Gutenberg University, Mainz, Germany.
FAU - van Ewijk, Reyn
AU  - van Ewijk R
AD  - Institute of Medical Biostatistics, Epidemiology and Informatics, University 
      Medical Center of Johannes Gutenberg University, Mainz, Germany.
FAU - Theobald, Matthias
AU  - Theobald M
AD  - Department of Medicine III, Hematology, Internal Oncology and Pneumology, 
      University Medical Center of Johannes Gutenberg University, Mainz, Germany.
FAU - Meyer, Ralf G
AU  - Meyer RG
AD  - Department of Medicine III, Hematology, Internal Oncology and Pneumology, 
      University Medical Center of Johannes Gutenberg University, Mainz, Germany.
FAU - Herr, Wolfgang
AU  - Herr W
AD  - Department of Medicine III, Hematology, Internal Oncology and Pneumology, 
      University Medical Center of Johannes Gutenberg University, Mainz, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131008
PL  - Netherlands
TA  - Exp Hematol
JT  - Experimental hematology
JID - 0402313
RN  - 0 (Antigens, CD34)
RN  - 0 (IL2RG protein, human)
RN  - 0 (Interleukin Receptor Common gamma Subunit)
SB  - IM
MH  - Animals
MH  - Antigens, CD34/*analysis
MH  - CD8-Positive T-Lymphocytes/*immunology
MH  - *Hematopoietic Stem Cell Transplantation
MH  - Herpesvirus 4, Human/*immunology
MH  - Histocompatibility Testing
MH  - Humans
MH  - *Immunologic Memory
MH  - Immunotherapy, Adoptive
MH  - Interleukin Receptor Common gamma Subunit/*physiology
MH  - Mice
MH  - Mice, SCID
MH  - T-Lymphocytes/*immunology
MH  - Transplantation, Homologous
EDAT- 2013/10/15 06:00
MHDA- 2014/02/11 06:00
CRDT- 2013/10/15 06:00
PHST- 2013/08/30 00:00 [received]
PHST- 2013/09/26 00:00 [accepted]
PHST- 2013/10/15 06:00 [entrez]
PHST- 2013/10/15 06:00 [pubmed]
PHST- 2014/02/11 06:00 [medline]
AID - S0301-472X(13)00753-4 [pii]
AID - 10.1016/j.exphem.2013.09.013 [doi]
PST - ppublish
SO  - Exp Hematol. 2014 Jan;42(1):28-38.e1-2. doi: 10.1016/j.exphem.2013.09.013. Epub 
      2013 Oct 8.