Ligation of CD28 by its natural ligand CD86 in the absence of TCR stimulation induces lipid raft polarization in human CD4 T cells
Ligation of CD28 by its natural ligand CD86 in the absence of TCR stimulation induces lipid raft polarization in human CD4 T cells
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DOI：
10.4049/jimmunol.175.12.7848
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发表时间：
2005-12-15
影响因子：
4.4
通讯作者：
Finkel, TH
中科院分区：
文献类型：
--
作者：
Kovacs, B;Parry, RV;Finkel, TH
用抗cd3 / cd28包被珠刺激静息CD4 T细胞可导致脂筏（LRs）的快速极化。据推测，共刺激的一个主要作用是促进LR聚集。CD86在多种自身免疫性疾病和感染性疾病的免疫细胞上上调或异常表达。利用CD86细胞外结构域（CD861g）与磁珠或表达CD86的K562细胞的Ig融合，我们证明了CD28由其天然配体连接，而不是由Ab连接，在没有TCR连接的情况下，在新鲜人CD4 T细胞的细胞头界面诱导LRs极化。这与Vav-1的激活、细胞内钙浓度的增加和NF-kappa bp65的核易位相关，但不导致T细胞增殖或细胞因子的产生。这些研究首次表明，LR极化可以在没有TCR触发的情况下发生，仅由CD28/CD86相互作用驱动。这一结果暗示了T细胞活化的机制。这一过程的异常可能改变T细胞和B细胞的耐受性和对感染的易感性。
Stimulation of resting CD4 T cells with anti-CD3/CD28-coated beads leads to rapid polarization of lipid rafts (LRs). It has been postulated that a major role of costimulation is to facilitate LR aggregation. CD86 is up-regulated or expressed aberrantly on immune cells in a wide array of autoimmune and infectious diseases. Using an Ig fusion with the extracellular domain of CD86 (CD861g) bound to a magnetic bead or K562 cells expressing CD86, we demonstrated that ligation of CD28 by its natural ligand, but not by Ab, induced polarization of LRs at the cell-bead interface of fresh human CD4 T cells in the absence of TCR ligation. This correlated with activation of Vav-1, increase of the intracellular calcium concentration, and nuclear translocation of NF-kappa B p65, but did not result in T cell proliferation or cytokine production. These studies show, for the first time, that LR polarization can occur in the absence of TCR triggering, driven solely by the CD28/CD86 interaction. This result has implications for mechanisms of T cell activation. Abnormalities in this process may alter T and B cell tolerance and susceptibility to infection.