PMID- 20861805
OWN - NLM
STAT- MEDLINE
DCOM- 20110107
LR  - 20231213
IS  - 1534-6080 (Electronic)
IS  - 0041-1337 (Linking)
VI  - 90
IP  - 11
DP  - 2010 Dec 15
TI  - Immunosuppression involving soluble CD83 induces tolerogenic dendritic cells that 
      prevent cardiac allograft rejection.
PG  - 1145-56
LID - 10.1097/TP.0b013e3181f95718 [doi]
AB  - BACKGROUND: Dendritic cells (DCs) are crucial regulators of immunity and 
      important in inducing and maintaining tolerance. Here, we investigated the 
      potential of a novel DC-immunomodulating agent, soluble CD83 (sCD83), in inducing 
      transplant tolerance. METHODS: We used the C3H-to-C57BL/6 mouse cardiac 
      transplantation model that exhibits a combination of severe cell-mediated 
      rejection and moderate antibody-mediated rejection and investigated whether sCD83 
      could augment a combination therapy consisting of Rapamycin (Rapa) and 
      anti-CD45RB monoclonal antibody (alpha-CD45) to prolong allograft survival. RESULTS: 
      Monotherapies consisting of Rapa and alpha-CD45 were incapable of preventing 
      rejection. However, all treatments involving sCD83 were capable of (1) 
      down-modulating expression of various DC surface molecules, such as major 
      histocompatibility complex class II and costimulatory molecules, (2) reducing the 
      allogeneic stimulatory capacity of the DCs, and (3) significantly inhibiting 
      antidonor antibody responses. Most striking results were observed in the triple 
      therapy-treated group, sCD83Rapaalpha-CD45, where cell-mediated rejection and 
      antibody-mediated rejection were abrogated for over 100 days. Donor-specific 
      tolerance was achieved in long-term surviving recipients, because donor skin 
      transplants were readily accepted for an additional 100 days, whereas third-party 
      skin grafts were rejected. Success of triple therapy treatment was accompanied by 
      enhancement of tolerogenic-DCs that conferred antigen-specific protection on 
      adoptive transfer to recipients of an allogeneic heart graft. CONCLUSIONS: Our 
      study revealed that sCD83 is capable of attenuating DC maturation and function, 
      and inducing donor-specific allograft tolerance, in the absence of toxicity. 
      Thus, sCD83 seems to be a safe and valuable counterpart to current DC-modulating 
      agents.
FAU - Ge, Wei
AU  - Ge W
AD  - Department of Surgery, University of Western Ontario, London, ON, Canada.
FAU - Arp, Jacqueline
AU  - Arp J
FAU - Lian, Dameng
AU  - Lian D
FAU - Liu, Weihua
AU  - Liu W
FAU - Baroja, Miren L
AU  - Baroja ML
FAU - Jiang, Jifu
AU  - Jiang J
FAU - Ramcharran, Siobhan
AU  - Ramcharran S
FAU - Eldeen, Firas Zahr
AU  - Eldeen FZ
FAU - Zinser, Elisabeth
AU  - Zinser E
FAU - Steinkasserer, Alexander
AU  - Steinkasserer A
FAU - Chou, Perry
AU  - Chou P
FAU - Brand, Stephen
AU  - Brand S
FAU - Nicolette, Charles
AU  - Nicolette C
FAU - Garcia, Bertha
AU  - Garcia B
FAU - Wang, Hao
AU  - Wang H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Transplantation
JT  - Transplantation
JID - 0132144
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antigens, CD)
RN  - 0 (CD11c Antigen)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (Immunoglobulins)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Recombinant Proteins)
RN  - EC 3.1.3.48 (Leukocyte Common Antigens)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Adoptive Transfer
MH  - Animals
MH  - Antibodies, Monoclonal/pharmacology
MH  - Antigens, CD/genetics/*pharmacology
MH  - CD11c Antigen/immunology
MH  - Dendritic Cells/*drug effects/immunology/transplantation
MH  - Drug Therapy, Combination
MH  - Graft Rejection/immunology/*prevention & control
MH  - Heart Transplantation/*immunology
MH  - Histocompatibility Antigens Class II/immunology
MH  - Humans
MH  - Immunity, Cellular/drug effects
MH  - Immunity, Humoral/drug effects
MH  - Immunoglobulins/genetics/*pharmacology
MH  - Immunophenotyping
MH  - Immunosuppressive Agents/*pharmacology
MH  - Leukocyte Common Antigens/immunology
MH  - Male
MH  - Membrane Glycoproteins/genetics/*pharmacology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C3H
MH  - Mice, Inbred C57BL
MH  - Protein Structure, Tertiary
MH  - Recombinant Proteins/pharmacology
MH  - Sirolimus/pharmacology
MH  - Skin Transplantation
MH  - Time Factors
MH  - Transplantation Tolerance/*drug effects
MH  - Transplantation, Homologous
MH  - CD83 Antigen
EDAT- 2010/09/24 06:00
MHDA- 2011/01/08 06:00
CRDT- 2010/09/24 06:00
PHST- 2010/09/24 06:00 [entrez]
PHST- 2010/09/24 06:00 [pubmed]
PHST- 2011/01/08 06:00 [medline]
AID - 10.1097/TP.0b013e3181f95718 [doi]
PST - ppublish
SO  - Transplantation. 2010 Dec 15;90(11):1145-56. doi: 10.1097/TP.0b013e3181f95718.