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Rapamycin selectively expands CD4(+)CD25(+)FoxP3(+) regulatory T cells
Rapamycin selectively expands CD4(+)CD25(+)FoxP3(+) regulatory T cells BLOOD Battaglia, M., Stabilini, A., Roncarolo, M. G. 2005; 105 (12): 4743-4748Abstract
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.
View details for DOI 10.1182/blood-2004-10-3932
View details for Web of Science ID 000229757300040
View details for PubMedID 15746082