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Blood, 15 June 2005, Vol. 105, No. 12, pp. 4743-4748.
Prepublished online as a Blood First Edition Paper on March 3, 2005; DOI 10.1182/blood-2004-10-3932.


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IMMUNOBIOLOGY

Rapamycin selectively expands CD4+CD25+FoxP3+ regulatory T cells

Manuela Battaglia, Angela Stabilini, and Maria-Grazia Roncarolo

From the San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), Milan, Italy; and Vita Salute San Raffaele University, Milan, Italy.

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. (Blood. 2005;105:4743-4748)


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