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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. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-10-3932v1 105/12/4743    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Battaglia, M. Articles by Roncarolo, M.-G. Search for Related Content PubMed PubMed Citation Articles by Battaglia, M. Articles by Roncarolo, M.-G. Related Collections Immunobiology Immunotherapy Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  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) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Ex vivo expansion of CD4+CD25+ T regulatory cells Elizabeth H. Field Blood 2005 105: 4542-4543. [Full Text] [PDF] This article has been cited by other articles: J. Mariotti, J. Foley, K. Ryan, N. Buxhoeveden, V. Kapoor, S. Amarnath, and D. H. Fowler Graft rejection as a Th1-type process amenable to regulation by donor Th2-type cells through an interleukin-4/STAT6 pathway Blood, December 1, 2008; 112(12): 4765 - 4775. [Abstract] [Full Text] [PDF] H. R. Turnquist, T. L. 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Lopez-Holgado, P. Maiso, M. Alberca, E. Villaron, et al. Bortezomib induces selective depletion of alloreactive T lymphocytes and decreases the production of Th1 cytokines Blood, May 1, 2006; 107(9): 3575 - 3583. [Abstract] [Full Text] [PDF] P.-Y. Mantel, N. Ouaked, B. Ruckert, C. Karagiannidis, R. Welz, K. Blaser, and C. B. Schmidt-Weber Molecular Mechanisms Underlying FOXP3 Induction in Human T Cells J. Immunol., March 15, 2006; 176(6): 3593 - 3602. [Abstract] [Full Text] [PDF] J. J. A. Coenen, H. J. P. M. Koenen, E. van Rijssen, L. B. Hilbrands, and I. Joosten Rapamycin, and not cyclosporin A, preserves the highly suppressive CD27+ subset of human CD4+CD25+ regulatory T cells Blood, February 1, 2006; 107(3): 1018 - 1023. [Abstract] [Full Text] [PDF] M. Battaglia, A. Stabilini, E. Draghici, S. Gregori, C. Mocchetti, E. Bonifacio, and M.-G. Roncarolo Rapamycin and Interleukin-10 Treatment Induces T Regulatory Type 1 Cells That Mediate Antigen-Specific Transplantation Tolerance Diabetes, January 1, 2006; 55(1): 40 - 49. [Abstract] [Full Text] [PDF] T. Muthukumar, D. Dadhania, R. Ding, C. Snopkowski, R. Naqvi, J. B. Lee, C. Hartono, B. Li, V. K. Sharma, S. V. Seshan, et al. Messenger RNA for FOXP3 in the urine of renal-allograft recipients. N. Engl. J. Med., December 1, 2005; 353(22): 2342 - 2351. [Abstract] [Full Text] [PDF]

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