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Rapamycin and IL-2 reduce lethal acute graft-versus-host disease associated with increased expansion of donor type CD4(+)CD25(+)Foxp3(+) regulatory T cells BLOOD Shin, H., Baker, J., Leveson-Gower, D. B., Smith, A. T., Sega, E. I., Negrin, R. S. 2011; 118 (8): 2342-2350

Abstract

Previous work has demonstrated that both rapamycin (RAPA) and IL-2 enhance CD4?CD25?Foxp3? regulatory T-cell (Treg) proliferation and function in vitro. We investigated whether the combination of RAPA plus IL-2 could impact acute GVHD induction after bone marrow transplantation (BMT). RAPA plus IL-2 resulted in improved survival and a reduction in acute GVHD lethality associated with an increased expansion of donor type CD4?Foxp3? Tregs and reduced CD4?CD25? conventional T cells (Tcons). RAPA plus IL-2, but not either drug alone, increased both expansion of donor natural Tregs and conversion of induced Tregs from donor CD25? Tcons while IL-2 alone increased conversion of Tregs from CD25? Tcon. RAPA plus IL-2 treatment resulted in less production of IFN-? and TNF, cytokines known to be important in the initiation of acute GVHD. These studies indicate that the pharmacologic stimulation of T cells with IL-2 and the suppression of Tcon proliferation with RAPA result in a selective expansion of functional Tregs and suppression of acute GVHD.

View details for DOI 10.1182/blood-2010-10-313684

View details for Web of Science ID 000294258000037

View details for PubMedID 21734238