PMID- 19034014
OWN - NLM
STAT- MEDLINE
DCOM- 20081231
LR  - 20181201
IS  - 1534-6080 (Electronic)
IS  - 0041-1337 (Linking)
VI  - 86
IP  - 10
DP  - 2008 Nov 27
TI  - Selective depletion of alloreactive T lymphocytes using patient-derived 
      nonhematopoietic stimulator cells in allograft engineering.
PG  - 1427-35
LID - 10.1097/TP.0b013e31818810d6 [doi]
AB  - BACKGROUND: Selective depletion of alloreactive T cells in vitro results in 
      efficient graft-versus-host disease prophylaxis in allogeneic hematopoietic 
      stem-cell transplantation, but it is accompanied by increased recurrence of 
      leukemia. To spare donor T-cell-mediated graft-versus-leukemia immunity against 
      hematopoiesis-restricted minor histocompatibility (minor-H) antigens, we explored 
      the use of patient-derived nonhematopoietic antigen-presenting cells (APC) as 
      allogeneic stimulators for selective allodepletion in leukemia-reactive donor 
      T-cell lines. METHODS: Primary keratinocytes, dermal fibroblasts, and bone marrow 
      fibroblasts were generated from skin biopsies and diagnostic bone marrow 
      aspirates of acute myeloid leukemia patients in vitro. Cell cultures were 
      analyzed for expansion, phenotype, and immunostimulatory capacity in comparison 
      with CD40-activated B cells as professional APC. In addition, nonhematopoietic 
      APCs were used for selective allodepletion in vitro. RESULTS: Patient-derived 
      fibroblasts could be reliably expanded to large cell numbers, whereas 
      keratinocytes had limited growth potential. Interferon-gamma-pretreated 
      fibroblasts showed increased expression of human leukocyte antigen (HLA)-class I 
      and II molecules, CD40, and CD54. Fibroblasts and CD40-activated B cells 
      comparably stimulated HLA-A*0301-specific CD8 T cells after transient expression 
      of HLA-A*0301 as a model alloantigen. Finally, fibroblasts could be effectively 
      applied to selectively deplete alloreactivity within leukemia-reactive donor CD8 
      T-cell lines by targeting the activation-induced antigen CD137. CONCLUSIONS: 
      Primary fibroblasts can be efficiently used as allogeneic nonhematopoietic APC 
      for selective depletion of donor T cells reactive to HLA and ubiquitously 
      expressed minor-H antigen disparities in leukemia-stimulated CD8 T-cell lines. 
      Therefore, harnessing alloreactivity to hematopoietic minor-H antigens in 
      addition to leukemia-associated antigens might increase graft-versus-leukemia 
      immunity of donor lymphocyte grafts in allogeneic hematopoietic stem-cell 
      transplantation.
FAU - Nonn, Marion
AU  - Nonn M
AD  - Department of Medicine III - Hematology and Oncology, Johannes 
      Gutenberg-University Medical School, Mainz, Germany.
FAU - Herr, Wolfgang
AU  - Herr W
FAU - Khan, Shamsul
AU  - Khan S
FAU - Todorova, Mariya
AU  - Todorova M
FAU - Link, Irina
AU  - Link I
FAU - Thies, Jochen
AU  - Thies J
FAU - Distler, Eva
AU  - Distler E
FAU - Kaltwasser, Marcus
AU  - Kaltwasser M
FAU - Hoffmann, Julia
AU  - Hoffmann J
FAU - Huber, Christoph
AU  - Huber C
FAU - Hartwig, Udo F
AU  - Hartwig UF
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Transplantation
JT  - Transplantation
JID - 0132144
RN  - 0 (Antigens, CD)
RN  - 0 (HLA-D Antigens)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Tumor Necrosis Factor Receptor Superfamily, Member 9)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Adult
MH  - Antigens, CD/immunology
MH  - B-Lymphocytes/immunology
MH  - Dermis/cytology/immunology
MH  - Epidermal Cells
MH  - Epidermis/immunology
MH  - Fibroblasts/drug effects/immunology
MH  - Graft vs Host Disease/immunology
MH  - HLA-D Antigens/immunology
MH  - Hematopoietic Stem Cell Transplantation/methods
MH  - Histocompatibility Antigens Class I/immunology
MH  - Humans
MH  - Interferon-gamma/immunology
MH  - Keratinocytes/immunology
MH  - Lymphocyte Depletion/*methods
MH  - Skin/immunology
MH  - T-Lymphocytes/*immunology
MH  - Tissue Engineering/methods
MH  - Transplantation, Homologous/*immunology
MH  - Tumor Necrosis Factor Receptor Superfamily, Member 9/immunology
EDAT- 2008/11/27 09:00
MHDA- 2009/01/01 09:00
CRDT- 2008/11/27 09:00
PHST- 2008/11/27 09:00 [pubmed]
PHST- 2009/01/01 09:00 [medline]
PHST- 2008/11/27 09:00 [entrez]
AID - 00007890-200811270-00016 [pii]
AID - 10.1097/TP.0b013e31818810d6 [doi]
PST - ppublish
SO  - Transplantation. 2008 Nov 27;86(10):1427-35. doi: 10.1097/TP.0b013e31818810d6.