TY - JOUR
T1 - Rapamycin selectively expands CD4+CD25+FoxP3 + regulatory T cells
AU - Battaglia, Manuela
AU - Stabilini, Angela
AU - Roncarolo, Maria Grazia
PY - 2005/6/15
Y1 - 2005/6/15
N2 - Rapamycin is an immunosuppressive compound that is currently used to prevent acute graft rejection in humans. In addition, rapamycin has been shown to allow operational tolerance in murine models. However, a direct effect of rapamycin on T regulatory (Tr) cells, which play a key role in induction and maintenance of peripheral tolerance, has not been demonstrated so far. Here, we provide new evidence that rapamycin selectively expands the murine naturally occurring CD4+CD25+FoxP3+ Tr cells in vitro. These expanded Tr cells suppress proliferation of syngeneic T cells in vitro and prevent allograft rejection in vivo. Interestingly, rapamycin does not block activation-induced cell death and proliferation of CD4+ T cells in vitro. Based on this new mode of action, rapamycin can be used to expand CD4+CD25+FoxP3+ Tr cells for ex vivo cellular therapy in T-cell-mediated diseases.
AB - Rapamycin is an immunosuppressive compound that is currently used to prevent acute graft rejection in humans. In addition, rapamycin has been shown to allow operational tolerance in murine models. However, a direct effect of rapamycin on T regulatory (Tr) cells, which play a key role in induction and maintenance of peripheral tolerance, has not been demonstrated so far. Here, we provide new evidence that rapamycin selectively expands the murine naturally occurring CD4+CD25+FoxP3+ Tr cells in vitro. These expanded Tr cells suppress proliferation of syngeneic T cells in vitro and prevent allograft rejection in vivo. Interestingly, rapamycin does not block activation-induced cell death and proliferation of CD4+ T cells in vitro. Based on this new mode of action, rapamycin can be used to expand CD4+CD25+FoxP3+ Tr cells for ex vivo cellular therapy in T-cell-mediated diseases.
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U2 - 10.1182/blood-2004-10-3932
DO - 10.1182/blood-2004-10-3932
M3 - Article
C2 - 15746082
AN - SCOPUS:20444373376
VL - 105
SP - 4743
EP - 4748
JO - Blood
JF - Blood
SN - 0006-4971
IS - 12
ER -