Orally tolerized T cells can form conjugates with APCs but are defective in immunological synapse formation
Orally tolerized T cells can form conjugates with APCs but are defective in immunological synapse formation
复制标题
DOI：
10.4049/jimmunol.175.2.829
复制
发表时间：
2005-07-15
影响因子：
4.4
通讯作者：
Hachimura, S
中科院分区：
文献类型：
--
作者：
Ise, W;Nakamura, K;Hachimura, S
口服免疫耐受是指口服可溶性抗原诱导的全身免疫低反应性。Ag特异性CD 4 T细胞的低反应性是造成这种现象的原因。然而，这些T细胞低反应状态的分子机制尚未完全了解。在本研究中，我们研究了口服耐受的T细胞与载银APC形成缀合物并将TCR、蛋白激酶C-θ（PKC-θ）和脂筏转运到T细胞和APC之间的界面的能力。口服耐受化的T细胞从OVA喂养的DO11.10小鼠的脾脏制备。有趣的是，口服耐受化的T细胞在与APC形成缀合物方面没有显示出任何损害。以LFA-1依赖性方式形成缀合物。在抗原刺激后，耐受化的T细胞确实可以激活Rap 1，这对LFA-1激活和细胞粘附至关重要。然而，口服耐受化的T细胞在TCR、PKC-θ和脂筏易位到T细胞和APC之间的界面中显示出缺陷。抗原刺激后TCR和PKC-θ向脂筏组分的易位也在耐受化T细胞中受损。银诱导的激活Vav，Rac 1，和cdc 42，这是必不可少的免疫突触和筏聚集，下调口服耐受的T细胞。这些结果表明，口服耐受化的T细胞可以在缀合物形成方面对特异性Ag应答，但不具有适当的免疫突触形成。这可以解释口服耐受化T细胞的低应答状态。
Oral tolerance is systemic immune hyporesponsiveness induced by the oral administration of soluble Ags. Hyporesponsiveness of Ag-specific CD4 T cells is responsible for this phenomenon. However, the molecular mechanisms underlying the hyporesponsive state of these T cells are not fully understood. In the present study, we investigated the ability of orally tolerized T cells to form conjugates with Ag-bearing APCs and to translocate TCR, protein kinase C-theta (PKC-theta), and lipid rafts into the interface between T cells and APCs. Orally tolerized T cells were prepared from the spleens of OVA-fed DO11.10 mice. Interestingly, the orally tolerized T cells did not show any impairment in the formation of conjugates with APCs. The conjugates were formed in a LFA-1-dependent manner. Upon antigenic stimulation, the tolerized T cells could indeed activate Rap1, which is critical for LFA-1 activation and thus cell adhesion. However, orally tolerized T cells showed defects in the translocation of TCR, PKC-theta, and lipid rafts into the interface between T cells and APCs. Translocation of TCR and PKC-theta to lipid raft fractions upon antigenic stimulation was also impaired in the tolerized T cells. Ag-induced activation of Vav, Rac1, and cdc42, which are essential for immunological synapse and raft aggregation, were down-regulated in orally tolerized T cells. These results demonstrate that orally tolerized T cells can respond to specific Ags in terms of conjugate formation but not with appropriate immunological synapse formation. This may account for the hyporesponsive state of orally tolerized T cells.