Division of Biological Sciences, University of Montana, Missoula, MT 59812, USA.
J Immunol. 2012 Nov 15;189(10):4728-39. doi: 10.4049/jimmunol.1201507. Epub 2012 Oct 12.
CD4(+) T cells capture membrane and membrane-bound molecules from APCs directly from the immunological synapse in a process termed trogocytosis. The function and biological consequences of trogocytosis are largely unknown. In this study, we examine the biological significance of this phenomenon on the trogocytosis-positive T cell. We used murine fibroblasts expressing GFP-tagged I-E(k) molecules loaded with a covalently attached antigenic peptide (moth cytochrome c 88-103) to present Ag to primary TCR transgenic T cells. Using a combination of high-resolution light microscopy and flow cytometry, we show that the trogocytosed molecules are retained on the surface of the T cell in association with the TCR and elevated phosphorylated ZAP-70, phosphorylated tyrosine, and phosphorylated ERK 1/2. Through the use of the Src inhibitor PP2, we demonstrate that trogocytosed molecules directly sustain TCR signaling. In addition, after removal of APC, trogocytosis-positive cells preferentially survive in culture over several days. These novel findings suggest that trogocytosed molecules continue to engage their receptors on the T cell surface and sustain intracellular signaling leading to selective survival of these cells.
CD4(+) T 细胞在免疫突触中直接从 APC 捕获膜和膜结合分子，这个过程称为细胞融合。细胞融合的功能和生物学后果在很大程度上是未知的。在这项研究中，我们研究了这种现象对融合阳性 T 细胞的生物学意义。我们使用表达 GFP 标记的 I-E(k)分子的小鼠成纤维细胞，这些分子装载有共价连接的抗原肽（蛾细胞色素 c88-103），以向原代 TCR 转基因 T 细胞呈递 Ag。我们结合高分辨率显微镜和流式细胞术，表明融合的分子与 TCR 一起保留在 T 细胞表面，并升高磷酸化 ZAP-70、磷酸化酪氨酸和磷酸化 ERK1/2。通过使用Src 抑制剂 PP2，我们证明融合的分子直接维持 TCR 信号。此外，在去除 APC 后，融合阳性细胞在培养中优先存活数天。这些新发现表明，融合的分子继续与其在 T 细胞表面的受体结合，并维持细胞内信号，导致这些细胞的选择性存活。
