gamma delta T-cell human glial cell interactions .2. Relationship between heat shock protein expression and susceptibility to cytolysis
gamma delta T-cell human glial cell interactions .2. Relationship between heat shock protein expression and susceptibility to cytolysis
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DOI：
10.1016/s0165-5728(96)00218-4
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发表时间：
1997-04-01
影响因子：
3.3
通讯作者：
Antel, JP
中科院分区：
文献类型：
--
作者：
Freedman, MS;Bitar, R;Antel, JP
γ δ T细胞可能通过与热休克蛋白（hsp）的相互作用而与多发性硬化（MS）的免疫发病机制有关。我们以前已经证明，人少突胶质细胞（OGC）表达热休克蛋白在其表面上，并诱导γ δ T细胞的增殖和扩张。我们还表明，γ δ T细胞在体外对OGC具有高度的细胞溶解性。目前的研究旨在解决γ δ T细胞诱导的对OGC的细胞毒性是否涉及OGC或其他一些配体上hsp的识别。我们首先比较了不同的人类神经胶质细胞的裂解潜力，发现γ δ T细胞裂解OGC，小胶质细胞和人类胎儿星形胶质细胞的程度相同，尽管优先表达的HSP只对OGC。这表明热休克蛋白不参与溶细胞识别，或者存在不止一种配体。为了解决这个问题，我们使用了在冷靶竞争测定中具有0GC特性的hsp表达和刺激γ δ T细胞的能力（RPMI 8226，Daudi）或不具有0GC特性的细胞系（U937）。结果表明，尽管所有细胞系都被γ δ T细胞有效地杀死，但只有RPMI 8226和Daudi细胞能够有效地与OGC竞争裂解。这些结果支持了这样的观点，即可能存在不止一种用于γ δ T细胞细胞毒性识别的配体，但热休克蛋白仍可能参与γ δ T细胞诱导的OGC裂解。因此，调节OGC上hsp的表达可能是干扰MS中潜在的γ δ T细胞诱导的损伤的一种方式。
gamma delta T-cells have been implicated in the immunopathogenesis of multiple sclerosis (MS), possibly through interaction with heat shock proteins (hsp). We have previously demonstrated that human oligodendrocytes (OGC) express hsp on their surface and induce the proliferation and expansion of gamma delta T-cells. We also showed that gamma delta T-cells are highly cytolytic to OGC in vitro. The current study addresses whether gamma delta T-cell-induced cytotoxicity to OGC involves the recognition of hsp on OGC or some other ligand. We first compared the lytic potential for different human glial cells and found that gamma delta T-cells lysed OGC, microglia and human fetal astrocytes to the same extent, despite the preferential expression of hsp only on OGC. This suggested that either hsp was not involved in cytolytic recognition or that more than one ligand exists. To address this we used cell lines that either shared OGC properties of hsp expression and the ability to stimulate gamma delta T-cells (RPMI 8226, Daudi) or did not (U937) in cold target competition assays with OGC. Results demonstrated that although all the cell lines were effectively killed by gamma delta T-cells, only the RPMI 8226 and Daudi cells were able to effectively compete for lysis with the OGC. These results support the notion that probably more than one ligand for gamma delta T-cell cytotoxic recognition exists but hsp could still be involved in gamma delta T-cell-induced lysis of OGC. Regulating the expression of hsp on OGC might therefore be a way of interfering with potential gamma delta T-cell-induced damage in MS.