PMID- 19393276
OWN - NLM
STAT- MEDLINE
DCOM- 20091013
LR  - 20131121
IS  - 1879-1166 (Electronic)
IS  - 0198-8859 (Linking)
VI  - 70
IP  - 7
DP  - 2009 Jul
TI  - Mitomycin C-treated antigen-presenting cells as a tool for control of allograft 
      rejection and autoimmunity: from bench to bedside.
PG  - 506-12
LID - 10.1016/j.humimm.2009.04.024 [doi]
AB  - Cells have been previously used in experimental models for tolerance induction in 
      organ transplantation and autoimmune diseases. One problem with the therapeutic 
      use of cells is standardization of their preparation. We discuss an 
      immunosuppressive strategy relying on cells irreversibly transformed by a 
      chemotherapeutic drug. Dendritic cells (DCs) of transplant donors pretreated with 
      mitomycin C (MMC) strongly prolonged rat heart allograft survival when injected 
      into recipients before transplantation. Likewise, MMC-DCs loaded with myelin 
      basic protein suppressed autoreactive T cells of MS patients in vitro and 
      prevented experimental autoimmune encephalitis in mice. Comprehensive gene 
      microarray analysis identified genes that possibly make up the suppressive 
      phenotype, comprising glucocorticoid leucine zipper, immunoglobulin-like 
      transcript 3, CD80, CD83, CD86, and apoptotic genes. Based on these findings, a 
      hypothetical model of tolerance induction by MMC-treated DCs is delineated. 
      Finally, we describe the first clinical application of MMC-treated 
      monocyte-enriched donor cells in an attempt to control the rejection of a 
      haploidentical stem cell transplant in a sensitized recipient and discuss the 
      pros and cons of using MMC-treated antigen-presenting cells for tolerance 
      induction. Although many questions remain, MMC-treated cells are a promising 
      clinical tool for controlling allograft rejection and deleterious immune 
      responses in autoimmune diseases.
FAU - Terness, Peter
AU  - Terness P
AD  - Institute of Immunology, University of Heidelberg, Department of Transplantation 
      Immunology, Heidelberg, Germany. peter.terness@med.uni-heidelberg.de
FAU - Kleist, Christian
AU  - Kleist C
FAU - Simon, Helmut
AU  - Simon H
FAU - Sandra-Petrescu, Flavius
AU  - Sandra-Petrescu F
FAU - Ehser, Sandra
AU  - Ehser S
FAU - Chuang, Jing-Jing
AU  - Chuang JJ
FAU - Mohr, Elisabeth
AU  - Mohr E
FAU - Jiga, Lucian
AU  - Jiga L
FAU - Greil, Johann
AU  - Greil J
FAU - Opelz, Gerhard
AU  - Opelz G
LA  - eng
PT  - Journal Article
DEP - 20090422
PL  - United States
TA  - Hum Immunol
JT  - Human immunology
JID - 8010936
RN  - 50SG953SK6 (Mitomycin)
SB  - IM
MH  - Adoptive Transfer
MH  - Animals
MH  - Antigen-Presenting Cells/drug effects/*immunology/transplantation
MH  - Apoptosis/immunology
MH  - Autoimmune Diseases/immunology/therapy
MH  - Autoimmunity/*immunology
MH  - Dendritic Cells/drug effects/immunology/transplantation
MH  - Graft Rejection/*immunology/therapy
MH  - Humans
MH  - Mitomycin/*pharmacology
MH  - Models, Immunological
MH  - Organ Transplantation/methods
MH  - T-Lymphocytes/immunology
MH  - Transplantation, Homologous
EDAT- 2009/04/28 09:00
MHDA- 2009/10/14 06:00
CRDT- 2009/04/28 09:00
PHST- 2009/03/24 00:00 [received]
PHST- 2009/04/15 00:00 [accepted]
PHST- 2009/04/28 09:00 [entrez]
PHST- 2009/04/28 09:00 [pubmed]
PHST- 2009/10/14 06:00 [medline]
AID - S0198-8859(09)00113-X [pii]
AID - 10.1016/j.humimm.2009.04.024 [doi]
PST - ppublish
SO  - Hum Immunol. 2009 Jul;70(7):506-12. doi: 10.1016/j.humimm.2009.04.024. Epub 2009 
      Apr 22.