The mean survival time of group D was longer than that of group C (P = 0·0039, Fig. 4c). The score of aGVHD in group D was lower than that in group C (P = 0·0422). We detected donor spleen Ferroptosis inhibition cell chimerism (H-2b) in the long-term surviving mice of group D by FACS. The donor mouse chimerism rate was 3·15 ± 1·59%, which is higher than that of normal BALB/C spleen cells (0·61 ± 0·32%) (P = 0·0062, Fig. 5b). Although the chimerism rate was much lower, we could

detected the chimerism by PCR again (Fig. 5a). The liver and small bowel of dead mice and the long-term surviving mice of group D following the observation period were taken for GVHD histological examination. The aGVHD histological manifestations in the long-term surviving group D mice were slight, such as the damage to sinus hepaticus endothelial cells and anabrosis of the mucous membrane Selleckchem Saracatinib of the small intestine (Fig. 6c and d). However, the histological manifestations

in those mice which died of aGVHD were serious, showing diffuse cellular swelling, degeneration of hepatic parenchymal cells and complete damage of the mucous membrane gland of the small intestine (Fig. 6e,f). IL-2 is the first T cell growth factor to be cloned molecularly and remains the cytokine of choice for the propagation of T cells in culture [37]. Because IL-2 can induce T cell expansion potently in vitro, it has been assumed for many years that IL-2 played an analogous role in amplifying T cell responses in vivo. This assumption led to the development of therapeutic strategies aimed at modulating IL-2 signal strength for clinical efficacy. On one hand, IL-2 itself is infused in patients with cancer or acquired immune deficiency syndrome (AIDS) to enhance T cell numbers and function [38,39]. On the other hand, antibodies to the IL-2R are used to inhibit IL-2 signalling to suppress rejection of the transplanted

organs [40]. These agents show clinical efficacy Dipeptidyl peptidase in some cases, lending support to the notion that IL-2 serves as an important T cell growth factor and can promote immunity in vivo. However, this notion is now being challenged. IL-2 is critical for the development and peripheral expansion of CD4+CD25+ regulatory T cells, which promote self-tolerance by suppressing T cell responses in vivo (for a review, see [41]). A short course of high-dose IL-2 [42], begun on the day of bone marrow transplantation, protects against GVHD. This inhibitory effect is directed against donor CD4+ cells, even though the mechanism has not yet been elucidated. In this study, our results showed that IL-2 can inhibit T lymphocyte immunity. The up-regulation of SOCS-3 mRNA induced by IL-2 played a critical role during this course.