Synaptic transfer by human γδ T cells stimulated with soluble or cellular antigens
Synaptic transfer by human γδ T cells stimulated with soluble or cellular antigens
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DOI：
10.4049/jimmunol.168.12.6336
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发表时间：
2002-06-15
影响因子：
4.4
通讯作者：
Fournié, JJ
中科院分区：
文献类型：
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作者：
Espinosa, E;Tabiasco, J;Fournié, JJ
B、α T和NK淋巴细胞与其靶建立免疫突触（IS）以使识别成为可能。靶细胞衍生的Ag与近端分子一起转移到效应细胞上似乎也通过突触发生。很少有人知道这种转移的分子基础，但它被认为是从Ag受体内化。由于人类γ δ T细胞识别可溶性非肽磷酸化抗原以及肿瘤细胞如Daudi，因此尚不清楚它们是否与靶细胞建立IS并从靶细胞提取分子。使用流式细胞术和共聚焦显微镜，我们在这项工作中显示，银刺激的人V γ 9/Vdelta 2 T细胞共轭，并执行从各种肿瘤细胞靶分子转移。分子转移似乎与IS建立相关，在可溶性或细胞Ag存在下以剂量依赖性方式演变，并且需要γ δ TCR连接、Src家族激酶信号传导和肌动蛋白细胞骨架的参与。尽管CD 45排斥表征了γ δ T细胞进行的IS，但未检测到γ δ TCR的明显加帽。由γ δ T细胞介导的突触转移涉及与同源抗原无关的靶分子，并且独立于靶细胞的MHC I类表达而发生。从这些观察结果中，我们得出结论，尽管γ δ T细胞活化的特殊功能，突触形成和分子转移的决定因素属于靶细胞的特征γ δ T细胞识别抗原。
B, alphabeta T, and NK lymphocytes establish immunological synapses (IS) with their targets to enable recognition. Transfer of target cell-derived Ags together with proximal molecules onto the effector cell appears also to occur through synapses. Little is known about the molecular basis of this transfer, but it is assumed to result from Ag receptor internalization. Because human gammadelta T cells recognize soluble nonpeptidic phosphoantigens as well as tumor cells such as Daudi, it is unknown whether they establish IS with, and extract molecules from, target cells. Using flow cytometry and confocal microscopy, we show in this work that Ag-stimulated human Vgamma9/Vdelta2 T cells conjugate to, and perform molecular transfer from, various tumor cell targets. The molecular transfer appears to be linked to IS establishment, evolves in a dose-dependent manner in the presence of either soluble or cellular Ag, and requires gammadelta TCR ligation, Src family kinase signaling, and participation of the actin cytoskeleton. Although CD45 exclusion characterized the IS performed by gammadelta T cells, no obvious capping of the gammadelta TCR was detected. The synaptic transfer mediated by gammadelta T cells involved target molecules unrelated to the cognate Ag and occurred independently of MHC class I expression by target cells. From these observations, we conclude thatm despite the particular features of gammadelta T cell activation, both synapse formation and molecular transfer of determinants belonging to target cell characterize gammadelta T cell recognition of Ags.