PMID- 22952868
OWN - NLM
STAT- MEDLINE
DCOM- 20130207
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 7
IP  - 8
DP  - 2012
TI  - Tolerance induction by exosomes from immature dendritic cells and rapamycin in a 
      mouse cardiac allograft model.
PG  - e44045
LID - 10.1371/journal.pone.0044045 [doi]
LID - e44045
AB  - BACKGROUND: Dendritic cells (DCs) release bioactive exosomes that play an 
      important role in immune regulation. Because they express low levels of class I 
      major histocompatibility complex (MHC) and co-stimulatory molecules, exosomes 
      derived from donor immature DCs (imDex) prolong allograft survival by inhibiting 
      T-cell activation. However, this effect is limited and does not induce 
      immunological tolerance when imDex are administered alone. Thus, we tested the 
      effect of combined treatment with donor imDex and low-dose rapamycin on inducing 
      tolerance in a mouse cardiac transplantation model. METHODS: ImDex were obtained 
      from the culture supernatant of immature DCs derived from donor mouse (C57BL/6) 
      bone marrow and were injected with suboptimal doses of rapamycin into recipient 
      mouse (BALB/c) before and after transplantation. The capacity of this treatment 
      to induce immune tolerance was analyzed in vitro and in vivo using the mouse 
      cardiac transplantation model. RESULTS: Donor imDex expressed moderate levels of 
      MHC class II and low levels of MHC class I and co-stimulatory molecules, but 
      neither imDex nor subtherapeutic rapamycin dose alone induced cardiac allograft 
      tolerance. Combined treatment with imDex and rapamycin, however, led to donor 
      specific cardiac allograft tolerance. This effect was accompanied by decreased 
      anti-donor antigen cellular response and an increased percentage of spleen 
      CD4(+)CD25(+) T cells in recipients. Furthermore, this donor specific tolerance 
      could be further transferred to naive allograft recipients through injection of 
      splenocytes, but not serum, from tolerant recipients. CONCLUSION: Combined with 
      immunosuppressive treatment, donor imDex can prolong cardiac allograft survival 
      and induce donor specific allograft tolerance.
FAU - Li, Xiao
AU  - Li X
AD  - Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical 
      University, Xi'an, Shaanxi Province, China.
FAU - Li, Jun-Jie
AU  - Li JJ
FAU - Yang, Jing-Yue
AU  - Yang JY
FAU - Wang, De-Sheng
AU  - Wang DS
FAU - Zhao, Wei
AU  - Zhao W
FAU - Song, Wen-Jie
AU  - Song WJ
FAU - Li, Wei-Min
AU  - Li WM
FAU - Wang, Jian-Feng
AU  - Wang JF
FAU - Han, Wei
AU  - Han W
FAU - Zhang, Zhuo-Chao
AU  - Zhang ZC
FAU - Yu, Yong
AU  - Yu Y
FAU - Cao, Da-Yong
AU  - Cao DY
FAU - Dou, Ke-Feng
AU  - Dou KF
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120829
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Antigens)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Interleukin-2 Receptor alpha Subunit)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Antigens/immunology
MH  - Blotting, Western
MH  - CD4-Positive T-Lymphocytes/drug effects/immunology
MH  - Cell Differentiation/*drug effects
MH  - Cell Proliferation/drug effects
MH  - Dendritic Cells/*cytology/drug effects/*immunology
MH  - Dose-Response Relationship, Drug
MH  - Exosomes/drug effects/*immunology
MH  - Flow Cytometry
MH  - Graft Rejection/immunology
MH  - Graft Survival/drug effects/immunology
MH  - *Heart Transplantation
MH  - Immune Tolerance/*drug effects
MH  - Immunosuppressive Agents/pharmacology
MH  - Interleukin-2 Receptor alpha Subunit/metabolism
MH  - Lymphocyte Activation/drug effects
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Models, Animal
MH  - Sirolimus/*pharmacology
MH  - Spleen/cytology/immunology
MH  - Transplantation, Homologous
PMC - PMC3430614
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2012/09/07 06:00
MHDA- 2013/02/08 06:00
PMCR- 2012/08/29
CRDT- 2012/09/07 06:00
PHST- 2012/05/08 00:00 [received]
PHST- 2012/08/01 00:00 [accepted]
PHST- 2012/09/07 06:00 [entrez]
PHST- 2012/09/07 06:00 [pubmed]
PHST- 2013/02/08 06:00 [medline]
PHST- 2012/08/29 00:00 [pmc-release]
AID - PONE-D-12-12950 [pii]
AID - 10.1371/journal.pone.0044045 [doi]
PST - ppublish
SO  - PLoS One. 2012;7(8):e44045. doi: 10.1371/journal.pone.0044045. Epub 2012 Aug 29.