PMID- 21439133
OWN - NLM
STAT- MEDLINE
DCOM- 20130619
LR  - 20211020
IS  - 1555-3892 (Electronic)
IS  - 0963-6897 (Print)
IS  - 0963-6897 (Linking)
VI  - 20
IP  - 11-12
DP  - 2011
TI  - Rapamycin generates graft-homing murine suppressor CD8(+) T cells that confer 
      donor-specific graft protection.
PG  - 1759-69
LID - 10.3727/096368911X566244 [doi]
AB  - It has been reported that rapamycin (RPM) can induce de novo conversion of the 
      conventional CD4(+)Foxp3(-) T cells into CD4(+)Foxp3(+) regulatory T cells 
      (iTregs) in transplantation setting. It is not clear whether RPM can similarly 
      generate suppressor CD8(+) T cells to facilitate graft acceptance. In this study, 
      we investigated the ability of short-term RPM treatment in promoting long-term 
      acceptance (LTA) of MHC-mismatched skin allografts by generating a CD8(+) 
      suppressor T-cell population. We found that CD4 knockout (KO) mice (in C57BL/6 
      background, H-2(b)) can promptly reject DBA/2 (H-2(d)) skin allografts with mean 
      survival time (MST) being 13 days (p < 0.01). However, a short course RPM 
      treatment in these animals induced LTA with graft MST longer than 100 days. 
      Adoptive transfer of CD8(+) T cells from LTA group into recombination-activating 
      gene 1 (Rag-1)-deficient mice provided donor-specific protection of DBA/2 skin 
      grafts against cotransferred conventional CD8(+) T cells. Functionally active 
      immunoregulatory CD8(+) T cells also resided in donor skin allografts. Eighteen 
      percent of CD8(+) suppressor T cells expressed CD28 as measured by flow 
      cytometry, and produced reduced levels of IFN-gamma, IL-2, and IL-10 in comparison to 
      CD8(+) effector T cells as measured by ELISA. It is unlikely that CD8(+) 
      suppressor T cells mediated graft protection via IL-10, as IL-10/Fc fusion 
      protein impaired RPM-induced LTA in CD4 KO mice. Our data supported the notion 
      that RPM-induced suppressor CD8(+) T cells home to the allograft and exert 
      donor-specific graft protection.
FAU - El Essawy, Basset
AU  - El Essawy B
AD  - Department of Medicine, Transplant Institute, Beth Israel Deaconess Medical 
      Center, Harvard Medical School, Boston, MA 02215, USA.
FAU - Putheti, Prabhakar
AU  - Putheti P
FAU - Gao, Wenda
AU  - Gao W
FAU - Strom, Terry B
AU  - Strom TB
LA  - eng
GR  - P01 AI041521/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20110325
PL  - United States
TA  - Cell Transplant
JT  - Cell transplantation
JID - 9208854
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Interleukin-2)
RN  - 130068-27-8 (Interleukin-10)
RN  - 82115-62-6 (Interferon-gamma)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - CD8-Positive T-Lymphocytes/cytology/*drug effects/metabolism
MH  - Cells, Cultured
MH  - Graft Rejection/mortality/*prevention & control
MH  - Graft Survival/drug effects
MH  - Immunosuppressive Agents/*pharmacology
MH  - Interferon-gamma/metabolism
MH  - Interleukin-10/metabolism
MH  - Interleukin-2/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Sirolimus/*pharmacology
MH  - Skin/pathology
MH  - Skin Transplantation
MH  - Transplantation, Homologous
PMC - PMC3779926
MID - NIHMS511192
EDAT- 2011/03/29 06:00
MHDA- 2013/06/20 06:00
PMCR- 2013/09/23
CRDT- 2011/03/29 06:00
PHST- 2011/03/29 06:00 [entrez]
PHST- 2011/03/29 06:00 [pubmed]
PHST- 2013/06/20 06:00 [medline]
PHST- 2013/09/23 00:00 [pmc-release]
AID - ct0213elessawyetal [pii]
AID - 10.3727/096368911X566244 [doi]
PST - ppublish
SO  - Cell Transplant. 2011;20(11-12):1759-69. doi: 10.3727/096368911X566244. Epub 2011 
      Mar 25.