MRL/Mp CD4+,CD25-T cells show reduced sensitivity to suppression by CD4+,CD25+regulatory T cells in vitro - A novel defect of T cell regulation in systemic lupus erythematosus
MRL/Mp CD4+,CD25-T cells show reduced sensitivity to suppression by CD4+,CD25+regulatory T cells in vitro - A novel defect of T cell regulation in systemic lupus erythematosus
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DOI：
10.1002/art.20976
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发表时间：
2005-04-01
影响因子：
--
通讯作者：
Garden, OA
中科院分区：
文献类型：
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作者：
Monk, CR;Spachidou, M;Garden, OA
Objective.目的探讨外周血CD 4+、CD 25+调节性T细胞介导的抑制功能丧失是系统性红斑狼疮（SLE）的标志。MRL/Mp品系小鼠作为SLE的多基因模型进行了研究。免疫磁性选择后，在抗CD 3/CD 28单克隆抗体包被的珠存在下单独或一起培养外周淋巴CD 25+和CD 25-CD 4 + T细胞。通过测量氚化胸苷的掺入来评估增殖。MRL/Mp CD 4+，CD 25+调节性T细胞在体外仅表现出轻微的调节功能异常，而同源性CD 4+，CD 25-T细胞对抑制的敏感性显著降低。我们的研究结果强调了SLE外周耐受的一个新缺陷。识别这种缺陷可能为治疗干预开辟新的机会。
Objective. To investigate the hypothesis that loss of suppression mediated by peripheral CD4+,CD25+ regulatory T cells is a hallmark of systemic lupus erythematosus (SLE).Methods. Mice of the MRL/Mp strain were studied as a pollygenic model of SLE. Following immunomagnetic selection, peripheral lymphoid CD25+ and CD25- CD4+ T cells were cultured independently or together in the presence of anti-CD3/CD28 monoclonal antibody-coated beads. Proliferation was assessed by measuring the incorporation of tritiated thymidine.Results. While MRL/Mp CD4+,CD25+ regulatory T cells showed only subtle abnormalities of regulatory function in vitro, syngeneic CD4+,CD25- T cells showed significantly reduced sensitivity to suppression, as determined by crossover experiments in which MRL/Mp CD4+,CD25- T cells were cultured with H-2-matched CBA/Ca CD4+,CD25+ regulatory T cells in the presence of a polyclonal stimulus.Conclusion. Our findings highlight a novel defect of peripheral tolerance in SLE. Identification of this defect could open new opportunities for therapeutic intervention.