Induction of autoimmunity by CD4+CD62Iow cells in vivo
Induction of autoimmunity by CD4+CD62Iow cells in vivo
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DOI：
10.4049/jimmunol.177.7.4384
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发表时间：
2006-10-01
影响因子：
4.4
通讯作者：
Bischof, Felix
中科院分区：
文献类型：
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作者：
Amend, Bastian;Doster, Hong;Bischof, Felix
决定自身免疫发展的自身特异性CD4(+) T细胞外周激活的先决条件尚不完全清楚。用髓磷脂蛋白-磷脂蛋白（PLP） 139-151免疫的SJL小鼠在免疫时注射百日咳毒素（PT），而在免疫6天后不注射，发生实验性自身免疫性脑脊髓炎（EAE），表明PT诱导的外周免疫反应改变导致自身免疫的发展。使用IA(s)/PLP139-151四聚体进一步分析发现，PT不改变效应T细胞活化或调节性T细胞数量，但通过自身特异性CD4(+) T细胞增强ifn - γ的产生。此外，PT促进体内CD4(+)CD62L（低）效应T细胞的生成。在过继性转移后，这些细胞比CD4(+)CD62L（高）细胞在诱导受体小鼠自身免疫方面更有效。该群体的产生与CD11c(+)CD4（+）树突状细胞上共刺激分子CD80、CD86和B7-DC的高表达并行，但不表达B7-RP、PD-1和B7-H1，而CD11c(+)CD8 α(+)树突状细胞没有改变。总的来说，这些数据证明了CD4(+)CD62L（低）细胞在体内特异性扩增诱导自身免疫，并表明CD4(+)CD62L（低）效应T细胞和CD11c(+)CD4（+）树突状细胞可能是免疫干预治疗自身免疫性疾病的有吸引力的靶点。
The prerequisites of peripheral activation of self-specific CD4(+) T cells that determine the development of autoimmunity are incompletely understood. SJL mice immunized with myelin proteolipid protein (PLP) 139-151 developed experimental autoimmune encephalomyelitis (EAE) when pertussis toxin (PT) was injected at the time of immunization but not when injected 6 days later, indicating that PT-induced alterations of the peripheral immune response lead to the development of autoimmunity. Further analysis using IA(s)/PLP139-151 tetramers revealed that PT did not change effector T cell activation or regulatory T cell numbers but enhanced IFN-gamma production by self-specific CD4(+) T cells. In addition, PT promoted the generation of CD4(+)CD62L(low) effector T cells in vivo. Upon adoptive transfer, these cells were more potent than CD4(+)CD62L(high) cells in inducing autoimmunity in recipient mice. The generation of this population was paralleled by higher expression of the costimulatory molecules CD80, CD86, and B7-DC, but not B7-RP, PD-1, and B7-H1 on CD11c(+)CD4(+) dendritic cells whereas CD11c(+)CD8 alpha(+) dendritic cells were not altered. Collectively, these data demonstrate the induction of autoimmunity by specific in vivo expansion of CD4(+)CD62L(low) cells and indicate that CD4(+)CD62L(low) effector T cells and CD11c(+)CD4(+) dendritic cells maybe attractive targets for immune interventions to treat autoimmune diseases.