免疫突触在CD4淋巴细胞的血统承诺中的作用
Roberto A Maldonado1, Darrell J Irvine, Robert Schreiber
1Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts 02115-6017, USA.
Nature
|September 24, 2004
概括
纯粹的T助手细胞分化成Th1或Th2是由受体相互作用指导的. 我们发现,干扰素-受体 (IFNGR) 与T细胞受体 (TCR) 的共极化指导细胞命运,这是由互白素-4 (IL-4) 调节的过程.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 分子信号传输的方法
背景情况:
- 纯粹的T辅助淋巴细胞 (Thp) 将其分化为Th1或Th2系是适应性免疫的关键.
- 来自T细胞,共刺激和细胞因子受体的信号在Thp谱系承诺中的整合尚未完全理解.
- 干扰素-受体 (IFNGR) 和介质素-4受体 (IL-4R) 是早期T-辅助细胞结合的关键调节者.
研究的目的:
- 研究 Thp 线路承诺期间的信号集成机制.
- 阐明细胞因子受体共极化在免疫突触中的作用.
- 解释介质素-4 (IL-4) 如何抑制Th1分化.
主要方法:
- 研究了IFNGR与T细胞受体 (TCR) 在Thp细胞参与时的共极化.
- 在Th1-prone (C57BL/6) 和Th2-prone (BALB/c) 的小鼠株中比较受体共极化.
- 研究了IL-4对IFNGR-TCR共极化的影响以及Stat6.6的作用.
主要成果:
- 在TCR接触时,在免疫突触内观察到IFNGR与TCR的快速共极化.
- 与 Th2-prone BALB/c Thp 细胞相比,Th1-prone C57BL/6 Thp 细胞发生了显著更高的 IFNGR-TCR 共极化.
- IL-4治疗以Stat6依赖的方式阻止IFNGR与TCR的共极化,这解释了IL-4抑制Th1分化.
结论:
- 关键受体的物理共极化,如IFNGR和TCR,指导天真的Thp细胞命运.
- 免疫突触在通过受体共极化指导细胞分化方面发挥着新的作用.
- 膜绑定信号控制的新机制涉及功能对抗性受体对受体领域的物理干扰.
相关概念视频
Lineage Commitment
Commitment is the process whereby stem cells:
Immunoglobulin-like Cell Adhesion Molecules
Immunoglobulin-like cell adhesion molecules or Ig-CAMs are a versatile group of cell surface glycoproteins belonging to the immunoglobulin protein superfamily. Ig-CAMs possess the characteristic immunoglobulin protein domains and other domains such as the fibronectin type III domain. The Ig domains are glycosylated to varying degrees in different Ig-CAMs.
Ig-CAMs exhibit either homophilic binding (to other Ig-CAMs) or heterophilic binding (to other ligands such as integrins). While most Ig-CAMs...
Ig-CAMs exhibit either homophilic binding (to other Ig-CAMs) or heterophilic binding (to other ligands such as integrins). While most Ig-CAMs...
Cells of the Adaptive Immune Response
The T and B lymphocytes of the adaptive immune system develop from common lymphoid progenitor cells in the bone marrow. These progenitors give rise to precursors that eventually develop into both T and B lymphocytes. As these precursors mature, they gain the ability to detect and respond to foreign antigens in the body, a process known as immunocompetence. Additionally, these precursors acquire self-tolerance, a process that ensures they do not react to self-antigens. This intricate system...
Diversity of Antigen Receptors
Antigen receptors are essential components of the immune system crucial in defending the body against foreign invaders. These receptors are present on the surface of B and T cells, enabling them to recognize antigens and mount an appropriate immune response.
Before encountering any antigen, lymphocytes express these receptors. On B cells, the antigen receptor is a membrane-bound antibody molecule called BCR; on T cells, it is a T cell receptor or TCR. B and T cell receptors are composed of two...
Before encountering any antigen, lymphocytes express these receptors. On B cells, the antigen receptor is a membrane-bound antibody molecule called BCR; on T cells, it is a T cell receptor or TCR. B and T cell receptors are composed of two...
T Cell Activation and Clonal Selection
T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...
Naive T cells that have not yet encountered an antigen express two primary CD...
B Cell Activation and Differentiation
The adaptive immune response, a sophisticated defense mechanism, relies on the activation and differentiation of B lymphocytes, or B cells. These processes enable our bodies to mount a tailored response against specific pathogens such as bacteria, free virus particles, toxins, and parasites.
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...


