PMID- 20626386
OWN - NLM
STAT- MEDLINE
DCOM- 20101115
LR  - 20230124
IS  - 1600-6143 (Electronic)
IS  - 1600-6135 (Print)
IS  - 1600-6135 (Linking)
VI  - 10
IP  - 8
DP  - 2010 Aug
TI  - Rapamycin-conditioned donor dendritic cells differentiate CD4CD25Foxp3 T cells in 
      vitro with TGF-beta1 for islet transplantation.
PG  - 1774-84
LID - 10.1111/j.1600-6143.2010.03199.x [doi]
AB  - Dendritic cells (DCs) conditioned with the mammalian target of rapamycin (mTOR) 
      inhibitor rapamycin have been previously shown to expand naturally existing 
      regulatory T cells (nTregs). This work addresses whether rapamycin-conditioned 
      donor DCs could effectively induce CD4(+)CD25(+)Foxp3(+) Tregs (iTregs) in cell 
      cultures with alloantigen specificities, and whether such in vitro-differentiated 
      CD4(+)CD25(+)Foxp3(+) iTregs could effectively control acute rejection in 
      allogeneic islet transplantation. We found that donor BALB/c bone marrow-derived 
      DCs (BMDCs) pharmacologically modified by the mTOR inhibitor rapamycin had 
      significantly enhanced ability to induce CD4(+)CD25(+)Foxp3(+) iTregs of 
      recipient origin (C57BL/6 (B6)) in vitro under Treg driving conditions compared 
      to unmodified BMDCs. These in vitro-induced CD4(+)CD25(+)Foxp3(+) iTregs exerted 
      donor-specific suppression in vitro, and prolonged allogeneic islet graft 
      survival in vivo in RAG(-/-) hosts upon coadoptive transfer with T-effector 
      cells. The CD4(+)CD25(+)Foxp3(+) iTregs expanded and preferentially maintained 
      Foxp3 expression in the graft draining lymph nodes. Finally, the 
      CD4(+)CD25(+)Foxp3(+) iTregs were further able to induce endogenous naive T cells 
      to convert to CD4(+)CD25(+)Foxp3(+) T cells. We conclude that 
      rapamycin-conditioned donor BMDCs can be exploited for efficient in vitro 
      differentiation of donor antigen-specific CD4(+)CD25(+)Foxp3(+) iTregs. Such in 
      vitro-generated donor-specific CD4(+)CD25(+)Foxp3(+) iTregs are able to 
      effectively control allogeneic islet graft rejection.
FAU - Pothoven, K L
AU  - Pothoven KL
AD  - Department of Medicine, Feinberg School of Medicine, Northwestern University, 
      Chicago, IL, USA.
FAU - Kheradmand, T
AU  - Kheradmand T
FAU - Yang, Q
AU  - Yang Q
FAU - Houlihan, J L
AU  - Houlihan JL
FAU - Zhang, H
AU  - Zhang H
FAU - Degutes, M
AU  - Degutes M
FAU - Miller, S D
AU  - Miller SD
FAU - Luo, X
AU  - Luo X
LA  - eng
GR  - DP2 DK083099/DK/NIDDK NIH HHS/United States
GR  - UL1 RR025741/RR/NCRR NIH HHS/United States
GR  - R01 NS026543/NS/NINDS NIH HHS/United States
GR  - K08 DK070029/DK/NIDDK NIH HHS/United States
GR  - 1K08DK070029-01/DK/NIDDK NIH HHS/United States
GR  - DP2DK083099-01/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20100712
PL  - United States
TA  - Am J Transplant
JT  - American journal of transplantation : official journal of the American Society of 
      Transplantation and the American Society of Transplant Surgeons
JID - 100968638
RN  - 0 (CD4 Antigens)
RN  - 0 (Forkhead Transcription Factors)
RN  - 0 (Foxp3 protein, mouse)
RN  - 0 (Il2ra protein, mouse)
RN  - 0 (Interleukin-2 Receptor alpha Subunit)
RN  - 0 (Transforming Growth Factor beta1)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - CD4 Antigens/*immunology
MH  - Cell Differentiation/drug effects/immunology
MH  - Dendritic Cells/drug effects/*immunology
MH  - Forkhead Transcription Factors/*immunology
MH  - Graft Rejection/immunology
MH  - Interleukin-2 Receptor alpha Subunit/*immunology
MH  - Islets of Langerhans Transplantation/immunology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Sirolimus/*pharmacology
MH  - T-Lymphocytes, Regulatory/*immunology
MH  - Transforming Growth Factor beta1/pharmacology
PMC - PMC3995630
MID - NIHMS570662
COIS- Conflict of Interest Statement The authors declare no conflict of interest.
EDAT- 2010/07/16 06:00
MHDA- 2010/11/16 06:00
PMCR- 2014/04/22
CRDT- 2010/07/15 06:00
PHST- 2010/07/15 06:00 [entrez]
PHST- 2010/07/16 06:00 [pubmed]
PHST- 2010/11/16 06:00 [medline]
PHST- 2014/04/22 00:00 [pmc-release]
AID - S1600-6135(22)14391-1 [pii]
AID - 10.1111/j.1600-6143.2010.03199.x [doi]
PST - ppublish
SO  - Am J Transplant. 2010 Aug;10(8):1774-84. doi: 10.1111/j.1600-6143.2010.03199.x. 
      Epub 2010 Jul 12.