期刊
CELL
卷 184, 期 15, 页码 3981-+出版社
CELL PRESS
DOI: 10.1016/j.cell.2021.05.028
关键词
-
资金
- Medical Scientist Training Program grant from the National Institute of General Medical Sciences of the NIH [T32GM007739]
- intramural research program of the National Institute of Allergy and Infectious Diseases, NIH
The study reveals that self-activated T cells in lymph nodes produce IL-2, enhancing local Treg proliferation and inhibitory function, forming a negative feedback loop. These micro-domain constraints result in transient clonal expansion followed by rapid death of self-activated T cells, maintaining immune homeostasis.
A fraction of mature T cells can be activated by peripheral self-antigens, potentially eliciting host autoimmunity. We investigated homeostatic control of self-activated T cells within unperturbed tissue environments by combining high-resolution multiplexed and volumetric imaging with computational modeling. In lymph nodes, self-activated T cells produced interleukin (IL)-2, which enhanced local regulatory T cell (Treg) proliferation and inhibitory functionality. The resulting micro-domains reciprocally constrained inputs required for damaging effector responses, including CD28 co-stimulation and IL-2 signaling, constituting a negative feedback circuit. Due to these local constraints, self-activated T cells underwent transient clonal expansion, followed by rapid death (``pruning''). Computational simulations and experimental manipulations revealed the feedback machinery's quantitative limits: modest reductions in Treg micro-domain density or functionality produced non-linear breakdowns in control, enabling self-activated T cells to subvert pruning. This fine-tuned, paracrine feedback process not only enforces immune homeostasis but also establishes a sharp boundary between autoimmune and host-protective T cell responses.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据