PMID- 18261837
OWN - NLM
STAT- MEDLINE
DCOM- 20080520
LR  - 20080317
IS  - 0301-472X (Print)
IS  - 0301-472X (Linking)
VI  - 36
IP  - 4
DP  - 2008 Apr
TI  - Acute myeloid leukemia (AML)-reactive cytotoxic T lymphocyte clones rapidly 
      expanded from CD8(+) CD62L((high)+) T cells of healthy donors prevent AML 
      engraftment in NOD/SCID IL2Rgamma(null) mice.
PG  - 451-63
LID - 10.1016/j.exphem.2007.12.011 [doi]
AB  - OBJECTIVE: Current in vitro techniques for isolating leukemia-reactive cytotoxic 
      T lymphocytes (CTLs) from healthy donors are of relatively low efficiency and 
      yield responder populations with unknown biological significance. This study 
      aimed at the development of a more reliable approach, allowing generation and 
      expansion of acute myeloid leukemia (AML)-reactive CTLs using primary in vitro 
      stimulation. MATERIALS AND METHODS: We established allogeneic mini-mixed 
      lymphocyte-leukemia cultures (mini-MLLCs) by stimulating donor CD8(+) T cells 
      with human leukocyte antigen (HLA) class I-matched AML blasts in microtiter 
      plates. Before culture, CD8(+) T cells were separated into CD62L((high)+) and 
      CD62L((low)+/neg) subsets enriched for naive/central memory and effector memory 
      cells, respectively. RESULTS: In eight different related and unrelated donor/AML 
      pairs, numerous CTL populations were isolated that specifically lysed myeloid 
      leukemias in association with various HLA-A, -B, or -C alleles. These CTLs 
      expressed T-cell receptors of single Vbeta-chain families, indicating their 
      clonal origin. The majority of CTL clones were obtained from mini-MLLCs initiated 
      with CD62L((high)+) cells. Using antigen-specific stimulation, multiple CTL 
      populations were amplified to 10(8)-10(10) cells within 6 to 8 weeks. Three of 
      four representative CTL clones were capable of completely preventing engraftment 
      of human primary AML blasts in nonobese diabetic/severe combined immune deficient 
      IL2Rgamma(null) mice. CONCLUSION: The mini-MLLC approach allows the efficient in 
      vitro expansion of AML-reactive CTL clones from CD8(+)CD62L((high)+) precursors 
      of healthy donors. These CTLs can inhibit leukemia engraftment in immunodeficient 
      mice, suggesting their potential biological relevance.
FAU - Distler, Eva
AU  - Distler E
AD  - Department of Medicine III-Hematology and Oncology, Johannes Gutenberg-University 
      of Mainz, Mainz, Germany.
FAU - Wolfel, Catherine
AU  - Wolfel C
FAU - Kohler, Sylvia
AU  - Kohler S
FAU - Nonn, Marion
AU  - Nonn M
FAU - Kaus, Nina
AU  - Kaus N
FAU - Schnurer, Elke
AU  - Schnurer E
FAU - Meyer, Ralf G
AU  - Meyer RG
FAU - Wehler, Thomas C
AU  - Wehler TC
FAU - Huber, Christoph
AU  - Huber C
FAU - Wolfel, Thomas
AU  - Wolfel T
FAU - Hartwig, Udo F
AU  - Hartwig UF
FAU - Herr, Wolfgang
AU  - Herr W
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080208
PL  - Netherlands
TA  - Exp Hematol
JT  - Experimental hematology
JID - 0402313
RN  - 0 (Interleukin Receptor Common gamma Subunit)
RN  - 126880-86-2 (L-Selectin)
SB  - IM
MH  - Alleles
MH  - Animals
MH  - CD8-Positive T-Lymphocytes/*cytology/metabolism
MH  - Cells, Cultured
MH  - Clone Cells
MH  - Cytotoxicity Tests, Immunologic
MH  - Genes, MHC Class I
MH  - Humans
MH  - Interleukin Receptor Common gamma Subunit/*genetics
MH  - L-Selectin/*biosynthesis
MH  - Leukemia, Myeloid, Acute/blood/*immunology/*prevention & control
MH  - Mice
MH  - Mice, Inbred NOD
MH  - Mice, Knockout
MH  - Mice, SCID
MH  - Neoplasm Transplantation
MH  - Reference Standards
MH  - T-Lymphocytes, Cytotoxic/cytology/immunology/*transplantation
EDAT- 2008/02/12 09:00
MHDA- 2008/05/21 09:00
CRDT- 2008/02/12 09:00
PHST- 2007/06/22 00:00 [received]
PHST- 2007/12/05 00:00 [revised]
PHST- 2007/12/17 00:00 [accepted]
PHST- 2008/02/12 09:00 [pubmed]
PHST- 2008/05/21 09:00 [medline]
PHST- 2008/02/12 09:00 [entrez]
AID - S0301-472X(07)00708-4 [pii]
AID - 10.1016/j.exphem.2007.12.011 [doi]
PST - ppublish
SO  - Exp Hematol. 2008 Apr;36(4):451-63. doi: 10.1016/j.exphem.2007.12.011. Epub 2008 
      Feb 8.