Thalidomide with blockade of co-stimulatory molecules prolongs the survival of alloantigen-primed mice with cardiac allografts

沙利度胺联合共刺激分子阻断剂可延长接受心脏移植的同种抗原致敏小鼠的存活期

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作者:Maoshu Zhu #, Yunhan Ma #, Kai Tan, Liyi Zhang, Zhaowei Wang, Yongsheng Li, Yingyu Chen, Junjun Guo, Guoliang Yan, Zhongquan Qi0

Background

Miscellaneous memory cell populations that exist before organ transplantation are crucial barriers to transplantation. In the present study, we used a skin-primed heart transplantation model in mouse to evaluate the abilities of Thalidomide (TD), alone or in combination with co-stimulatory blockade, using monoclonal antibodies (mAbs) against memory T cells and alloantibodies to prolong the second cardiac survival.

Conclusions

Our study indicated a potential synergistic action of TD in combination with with mAbs to suppress the function of memory T cells and increase the survival of second allografts in alloantigen-primed mice.

Results

In the skin-primed heart transplantation model, TD combined with mAbs significantly prolonged the second cardiac survival, accompanied by inhibition of memory CD8+ T cells. This combined treatment enhanced the CD4+Foxp3+ regulatory T cells ratio in the spleen, restrained the infiltration of lymphocytes into the allograft, and suppressed the allo-response of spleen T cells in the recipient. The levels of allo-antibodies also decreased in the recipient serum. In addition, we detected low levels of the constitutions of the lytic machinery of cytotoxic cells, which cause allograft damage. Conclusions: Our study indicated a potential synergistic action of TD in combination with with mAbs to suppress the function of memory T cells and increase the survival of second allografts in alloantigen-primed mice.

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