Maria Sklodowska-Curie National Research Institute of Oncology, 44-102 Gliwice, Poland.
UPMC Hillman Cancer Center, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15232, USA.
Cells. 2022 Jun 18;11(12):1965. doi: 10.3390/cells11121965.
Exosomes that are released by T cells are key messengers involved in immune regulation. However, the molecular profiling of these vesicles, which is necessary for understanding their functions, requires their isolation from a very heterogeneous mixture of extracellular vesicles that are present in the human plasma. It has been shown that exosomes that are produced by T cells could be isolated from plasma by immune capture using antibodies that target the CD3 antigen, which is a key component of the TCR complex that is present in all T lymphocytes. Here, we demonstrate that CD3(+) exosomes that are isolated from plasma can be used for high-throughput molecular profiling using proteomics and metabolomics tools. This profiling allowed for the identification of proteins and metabolites that differentiated the CD3(+) from the CD3(-) exosome fractions that were present in the plasma of healthy donors. Importantly, the proteins and metabolites that accumulated in the CD3(+) vesicles reflected the known molecular features of T lymphocytes. Hence, CD3(+) exosomes that are isolated from human plasma by immune capture could serve as a "T cell biopsy".
T 细胞释放的细胞外囊泡是参与免疫调节的关键信使。然而，为了了解其功能，需要对这些囊泡进行分子分析，这就需要将其从人血浆中存在的非常异质的细胞外囊泡混合物中分离出来。已经表明，可以使用针对 TCR 复合物中存在的所有 T 淋巴细胞的关键组成部分 CD3 抗原的抗体通过免疫捕获从血浆中分离出由 T 细胞产生的细胞外囊泡。在这里，我们证明可以使用蛋白质组学和代谢组学工具对从血浆中分离出的 CD3(+)细胞外囊泡进行高通量分子分析。这种分析能够鉴定出区分来自健康供体血浆的 CD3(+)和 CD3(-)细胞外囊泡部分的蛋白质和代谢物。重要的是，在 CD3(+)囊泡中积累的蛋白质和代谢物反映了 T 淋巴细胞的已知分子特征。因此，通过免疫捕获从人血浆中分离的 CD3(+)细胞外囊泡可以作为“T 细胞活检”。
