诱导多能干干细胞中免疫突触分子的淘汰使T细胞后代能够获得广泛的NK细胞抵抗力
Jing Zhang1, Keisuke Sumide1, Keitaro Kanie1
1Shin Kaneko Laboratory, Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan.
Regenerative therapy
|January 26, 2026
概括
缺乏CD54和CD58的工程IPSC衍生的T细胞对自然杀手细胞的攻击表现出抵抗力. 这种通用免疫逃避策略通过克服免疫排斥和改善NK细胞逃避来增强T细胞疗法的潜力.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 再生医学是一种再生医学.
背景情况:
- 异构诱导多能干细胞 (iPSCs) 提供了再生T细胞疗法的潜力,但由于人类白细胞抗原 (HLA) 不相容而面临免疫排斥.
- 淘汰β2-微球蛋白 (B2M) 会降低HLA类I表达,防止CD8+T细胞死亡,但矛盾的是,通过"失踪自我"反应激活自然杀手 (NK) 细胞.
- 目前针对NK细胞逃避的策略是部分有效的,这是由于NK受体的多样性.
研究的目的:
- 通过向免疫突触 (IS) 粘附分子,为iPSC衍生的T细胞 (iT细胞) 开发一种通用免疫逃避策略.
- 为了设计缺乏CD54 (ICAM-1) 和CD58 (LFA-3) 的iT细胞,以破坏NK细胞的参与并增强免疫逃避.
主要方法:
- 利用CRISPR/Cas9基因编辑来创建缺少CD54和CD58的双击 (dKO) iT细胞.
- 建立在以前建立的低免疫性IT细胞平台 (B2MKOCIITAKOPVRKO与HLA-E过度表达) 上.
- 向的CD54和CD58,参与稳定NK向免疫突触的关键配体.
主要成果:
- 使用人类IL-15转基因小鼠模型,dKO iT细胞在体外和体内对NK细胞中介的细胞毒性表现出显著的抵抗力.
- 改造的iT细胞保持了它们的细胞毒性效应因子功能.
- 破坏NK参与的物理接口为各种NK细胞子集提供了广泛的保护.
结论:
- 建立了一个多功能平台,用于生成通用,抗NK的iT细胞.
- 这种方法补充了现有的以HLA为重点的免疫逃避策略.
- 通过改善NK细胞逃避,提高了基于iPSC的免疫疗法的转化潜力.
相关概念视频
Induced Pluripotent Stem Cells
28.0K
Stem cells are undifferentiated cells that divide and produce different types of cells. Ordinarily, cells that have differentiated into a specific cell type are post-mitotic—that is, they no longer divide. However, scientists have found a way to reprogram these mature cells so that they “de-differentiate” and return to an unspecialized, proliferative state. These cells are also pluripotent like embryonic stem cells—able to produce all cell types—and are therefore...
28.0K
Induced Pluripotent Stem Cells
5.5K
Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic...
Somatic...
5.5K
Immune Surveillance by NK Cells and Phagocytes
8.6K
Immune surveillance is an integral part of the innate immune system, involving the continuous monitoring of peripheral tissues to detect and respond to pathogens, infected cells, or cancerous cells. This surveillance is conducted primarily by natural killer (NK) cells and phagocytes, which employ distinct but complementary mechanisms to identify and eliminate threats.
Natural Killer Cells: The Fast Responders
NK cells are large granular lymphocytes found in the blood and lymphatic system. These...
Natural Killer Cells: The Fast Responders
NK cells are large granular lymphocytes found in the blood and lymphatic system. These...
8.6K
Adult Stem Cells
33.8K
Stem cells are undifferentiated cells that divide and produce more stem cells or progenitor cells that differentiate into mature, specialized cell types. All the cells in the body are generated from stem cells in the early embryo, but small populations of stem cells are also present in many adult tissues including the bone marrow, brain, skin, and gut. These adult stem cells typically produce the various cell types found in that tissue—to replace cells that are damaged or to continuously...
33.8K
Embryonic Stem Cells
32.3K
Embryonic stem (ES) cells are undifferentiated pluripotent cells, meaning they can produce any cell type in the body. This gives them tremendous potential in science and medicine since they can generate specific cell types for use in research or to replace body cells lost due to damage or disease.
32.3K
The Synapse
133.0K
Neurons communicate with one another by passing on their electrical signals to other neurons. A synapse is the location where two neurons meet to exchange signals. At the synapse, the neuron that sends the signal is called the presynaptic cell, while the neuron that receives the message is called the postsynaptic cell. Note that most neurons can be both presynaptic and postsynaptic, as they both transmit and receive information.
133.0K


