PMID- 22539294
OWN - NLM
STAT- MEDLINE
DCOM- 20120706
LR  - 20131121
IS  - 1521-4141 (Electronic)
IS  - 0014-2980 (Linking)
VI  - 42
IP  - 5
DP  - 2012 May
TI  - Double negative Treg cells promote nonmyeloablative bone marrow chimerism by 
      inducing T-cell clonal deletion and suppressing NK cell function.
PG  - 1216-25
LID - 10.1002/eji.201141808 [doi]
AB  - The establishment of immune tolerance and prevention of chronic rejection remain 
      major goals in clinical transplantation. In bone marrow (BM) transplantation, T 
      cells and NK cells play important roles for graft rejection. In addition, 
      graft-versus-host-disease (GVHD) remains a major obstacle for BM transplantation. 
      In this study, we aimed to establish mixed chimerism in an irradiation-free 
      condition. Our data indicate that adoptive transfer of donor-derived T-cell 
      receptor (TCR) alphabeta(+) CD3(+) CD4(-) CD8(-) NK1.1(-) (double negative, DN) Treg 
      cells prior to C57BL/6 to BALB/c BM transplantation, in combination with 
      cyclophosphamide, induced a stable-mixed chimerism and acceptance of C57BL/6 skin 
      allografts but rejection of third-party C3H (H-2k) skin grafts. Adoptive transfer 
      of CD4(+) and CD8(+) T cells, but not DN Treg cells, induced GVHD in this 
      regimen. The recipient T-cell alloreactive responsiveness was reduced in the DN 
      Treg cell-treated group and clonal deletions of TCRVbeta2, 7, 8.1/2, and 8.3 were 
      observed in both CD4(+) and CD8(+) T cells. Furthermore, DN Treg-cell treatment 
      suppressed NK cell-mediated BM rejection in a perforin-dependent manner. Taken 
      together, our results suggest that adoptive transfer of DN Treg cells can control 
      both adoptive and innate immunities and promote stable-mixed chimerism and 
      donor-specific tolerance in the irradiation-free regimen.
CI  - (c) 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
FAU - Su, Ye
AU  - Su Y
AD  - The Multi-Organ Transplant Program, London Health Sciences Centre, London, 
      Ontario, Canada.
FAU - Huang, Xuyan
AU  - Huang X
FAU - Wang, Shuang
AU  - Wang S
FAU - Min, Wei-Ping
AU  - Min WP
FAU - Yin, Ziqin
AU  - Yin Z
FAU - Jevnikar, Anthony M
AU  - Jevnikar AM
FAU - Zhang, Zhu-Xu
AU  - Zhang ZX
LA  - eng
GR  - Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Germany
TA  - Eur J Immunol
JT  - European journal of immunology
JID - 1273201
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - 126465-35-8 (Perforin)
RN  - 8N3DW7272P (Cyclophosphamide)
SB  - IM
MH  - Adoptive Transfer
MH  - Animals
MH  - Bone Marrow Transplantation/immunology
MH  - CD4-Positive T-Lymphocytes/drug effects/*immunology
MH  - CD8-Positive T-Lymphocytes/drug effects/*immunology
MH  - Chimerism/*drug effects
MH  - Clonal Deletion/drug effects/*immunology
MH  - Cyclophosphamide/therapeutic use
MH  - Graft vs Host Disease/drug therapy/immunology
MH  - Immunosuppressive Agents/therapeutic use
MH  - Killer Cells, Natural/drug effects/*immunology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Perforin/immunology
MH  - Receptors, Antigen, T-Cell/immunology
MH  - Skin Transplantation/immunology
MH  - T-Lymphocytes, Regulatory/drug effects/*immunology
EDAT- 2012/04/28 06:00
MHDA- 2012/07/07 06:00
CRDT- 2012/04/28 06:00
PHST- 2012/04/28 06:00 [entrez]
PHST- 2012/04/28 06:00 [pubmed]
PHST- 2012/07/07 06:00 [medline]
AID - 10.1002/eji.201141808 [doi]
PST - ppublish
SO  - Eur J Immunol. 2012 May;42(5):1216-25. doi: 10.1002/eji.201141808.