Targeted rapamycin treatment starting at the first detection of peripheral blood (PB) alloreactive T cells prevents lethal acute graft-versus-host disease (aGVHD). (A) Treatment was started as soon as alloreactive T cells could be identified in the PB based on their surface receptor profile. Scheme indicates time course of repeated rapamycin injections. Ventral and lateral bioluminescence imaging (BLI) images of representative mice per group (n = 5) are displayed. On days +15 and +21, signal thresholds were increased to resolve the predominant organ distribution of donor T cells. (B) BLI signals significantly decreased on days +11 and +15 in treated mice compared to vehicle controls (n = 5). Error bars display means plus or minus SEM. *P ≤0.05. (C) All rapamycin-treated mice (■) showed limited signs of aGVHD (left panel) on day +21 but rapidly and fully recovered. All rapamycin-treated mice survived (right panel) until the end of the experiment (day +100). In contrast, vehicle controls (◯) developed increasing signs of aGVHD starting by day +21 and 60% succumbed to aGVHD up to day +100. Mice that received lethal irradiation without subsequent hematopoietic cell transplantation (HCT) died of the consequences of myeloablation (×). Animals that received transplants of bone marrow alone did not show any clinical signs of aGVHD and survived (△). One experiment out of two is shown (n = 5).
Bäuerlein et al. BMC Medicine 2013 11:134 doi:10.1186/1741-7015-11-134