加州大学Matthew F. Krummel小组在研究中取得进展。他们揭示了巨噬细胞对活细胞进行亚微米取样。这一研究成果发表在2026年4月29日出版的国际学术期刊《自然》上。

在这里，课题组以一系列伴随成像和囊泡标记技术为主题，揭示了巨噬细胞进行的另一种过程，这种过程导致了对活细胞的非破坏性直接采样。这一过程需要细胞间接触，不需要半胱天冬酶激活，并通过靶细胞向巨噬细胞的类似巨噬细胞分裂的拉伸发生，从而产生含有细胞质的亚微米大小的囊泡。使用基于高维流动的方法标记囊泡，研究人员证明了活样材料经过明显处理，并且很难受到溶酶体离子的影响。这种材料也会对抗原向CD4 T细胞的呈递产生不同的影响。与CD8 T细胞相比通过将抗原重定向到溶酶体来破坏这种运输，可显著降低相关巨噬细胞介导的CD8 T细胞的启动。这些结果表明，免疫系统对活细胞进行了重要而大量的采样，对维持免疫边界具有明显的影响。

研究人员表示，一个有效的免疫系统需要采集和发展健康的自我认同，以防止自身免疫和识别致病性胰岛素。自体蛋白呈递给T在免疫细胞发育过程中，胸腺细胞中的细胞和它们可能会出现在全身各处，以维持调节性T细胞群，并提供滋补信号以维持常规的T细胞随时间变化。在一些器官中观察到持续的细胞凋亡以及骨髓细胞对这种物质的摄入，这导致了一种传统的理解，即持续的细胞死亡是自身抗原的主要原因。

附：英文原文

Title: Submicrometre sampling of living cells by macrophages

Author: Fan, Amy C., Thota, Rukman R., Serwas, Nina, Vykunta, Vivasvan S., Marchuk, Kyle, Ruhland, Megan K., Liu, Lauren, Johnson, Grace, Edwards, Austin, Krummel, Matthew F.

Issue&Volume: 2026-04-29

Abstract: An effective immune system must sample and develop healthy self-identity to prevent autoimmunity and to discern pathogenic insults1,2,3. Self-proteins are presented to Tcells in the thymus during immune cell development2,3 and must be presented throughout the body to maintain regulatory Tcell populations4,5,6 and to provide tonic signals to sustain conventional Tcells over time7,8,9. Observations of continuous apoptosis in some organs together with the ingestion of that material by myeloid populations has led to a conventional understanding of ongoing cell death as a major source of self-antigens10. Here we used a series of companion imaging and vesicular labelling technologies to reveal an alternative process undertaken by macrophages that results in non-destructive, direct sampling of living cells. This process requires cell–cell contact, does not require caspase activation and occurs via trogocytosis-like stretching of the target cell into the macrophage, which leads to the generation of submicrometre-sized vesicles that contain cytoplasm. Using a high-dimensional flow-based method for labelling vesicles, we demonstrate that live-sampled material is distinctly processed and is poorly subjected to fusion with lysosomes. The material also produces differential effects on the presentation of antigen to CD4 Tcells compared with CD8 Tcells. Disruption of this trafficking by redirecting antigen to the lysosome significantly reduced the associated macrophage-mediated priming of CD8 Tcells. These results demonstrate an important and substantial sampling of living cells by the immune system, with clear consequences for maintaining the border of immunity.

DOI: 10.1038/s41586-026-10435-5

Source: https://www.nature.com/articles/s41586-026-10435-5