Qu Yanyan, Zhang Baojun, Zhao Liang, Liu Guangwei, Ma Haixia, Rao Enyu, Zeng Chun, Zhao Yong
Transplantation Biology Research Division, State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beisihuan Xi Road 25, Beijing, 100080, China.
Transpl Immunol. 2007 Apr;17(3):153-61. doi: 10.1016/j.trim.2007.01.002. Epub 2007 Jan 24.
CD4(+)CD25(+)Regulatory T (Treg) cells are crucial for negatively regulating immune responses. Rapamycin (rapa) is an immunosuppressive agent which is widely used for preventing acute graft rejection in patients and has been used to induce operational tolerance in mouse models. The aim of the present study was to determine the effect of rapa on CD4(+)CD25(+)Foxp3(+)Treg cells in a mouse model. After C57BL/6 mice were intraperitoneally given 1.5 mg/kg/day of rapa for 14 days, the percentages, cell numbers, phenotype and function of CD4(+)CD25(+)Treg cells were determined by flow cytometry as well as the in vitro and in vivo functional assays. The cell numbers of CD4(+) and CD4(+)CD25(+)Treg cell subsets were markedly decreased in rapa-treated mice as reported. However, rapa significantly enhanced the ratios of CD4(+)CD25(+)Treg cells or CD4(+)CD25(+)Foxp3(+)Treg cells to CD4(+)T cells in spleens and thymi of mice (P<0.01) respectively. Furthermore, splenic CD4(+)CD25(+)Treg cells in rapa-treated mice showed immunosuppressive ability on the immune response of T effector cells to alloantigens or mitogen as efficiently as the control CD4(+)CD25(+)Treg cells in vitro and in vivo. Thus, rapa could significantly enhance the percentages of CD4(+)CD25(+)Foxp3(+)Treg cells in the thymus and the periphery while keeping these cells functional, indicating that CD4(+)CD25(+)Treg cells are more resistant to rapa than other CD4(+)T cells. The different effects of rapa on CD4(+)CD25(+)Treg and T effector cells make rapa to be a favorable choice for inducing immune tolerance to self-, allo-, or xeno-antigens.
CD4(+)CD25(+)调节性T（Treg）细胞对于负向调节免疫反应至关重要。雷帕霉素（rapa）是一种免疫抑制剂，广泛用于预防患者的急性移植物排斥反应，并已用于在小鼠模型中诱导操作性耐受。本研究的目的是确定rapa对小鼠模型中CD4(+)CD25(+)Foxp3(+)Treg细胞的影响。C57BL/6小鼠腹腔注射1.5mg/kg/天的rapa，持续14天，然后通过流式细胞术以及体外和体内功能测定来确定CD4(+)CD25(+)Treg细胞的百分比、细胞数量、表型和功能。如报道的那样，rapa处理的小鼠中CD4(+)和CD4(+)CD25(+)Treg细胞亚群的细胞数量明显减少。然而，rapa分别显著提高了小鼠脾脏和胸腺中CD4(+)CD25(+)Treg细胞或CD4(+)CD25(+)Foxp3(+)Treg细胞与CD4(+)T细胞的比例（P<0.01）。此外，rapa处理的小鼠脾脏CD4(+)CD25(+)Treg细胞在体外和体内对T效应细胞对同种异体抗原或丝裂原的免疫反应均显示出与对照CD4(+)CD25(+)Treg细胞一样有效的免疫抑制能力。因此，rapa可以显著提高胸腺和外周中CD4(+)CD25(+)Foxp3(+)Treg细胞的百分比，同时保持这些细胞的功能，表明CD4(+)CD25(+)Treg细胞比其他CD4(+)T细胞对rapa更具抗性。rapa对CD4(+)CD25(+)Treg和T效应细胞的不同作用使rapa成为诱导对自身、同种异体或异种抗原免疫耐受的理想选择。
