Department of Cancer Immunology & AIDS, Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA.
Nature. 2010 Sep 16;467(7313):328-32. doi: 10.1038/nature09370.
The ability to produce vigorous immune responses that spare self tissues and organs depends on the elimination of autoreactive T and B cells. However, purging of immature and mature self-reactive T and B cells is incomplete and may also require the involvement of cells programmed to suppress immune responses. Regulatory T cells (T(reg)) belonging to the CD4(+) T-cell subset may have a role in preventing untoward inflammatory responses, but T-cell subsets programmed to inhibit the development of autoantibody formation and systemic-lupus-erythematosus-like disease have not yet been defined. Here we delineate a CD8(+) regulatory T-cell lineage that is essential for the maintenance of self tolerance and prevention of murine autoimmune disease. Genetic disruption of the inhibitory interaction between these CD8(+) T cells and their target Qa-1(+) follicular T-helper cells results in the development of a lethal systemic-lupus-erythematosus-like autoimmune disease. These findings define a sublineage of CD8 T cells programmed to suppress rather than activate immunity that represents an essential regulatory element of the immune response and a guarantor of self tolerance.
产生免于自身组织和器官的强烈免疫反应的能力取决于清除自身反应性 T 和 B 细胞。然而，不成熟和成熟的自身反应性 T 和 B 细胞的清除并不完全，也可能需要涉及到被编程以抑制免疫反应的细胞。属于 CD4+T 细胞亚群的调节性 T 细胞（T(reg)）可能在预防不利的炎症反应方面发挥作用，但尚未定义被编程以抑制自身抗体形成和全身性红斑狼疮样疾病发展的 T 细胞亚群。在这里，我们描绘了一个 CD8+调节性 T 细胞谱系，它对于维持自身耐受和预防小鼠自身免疫性疾病至关重要。抑制这些 CD8+T 细胞与其靶 Qa-1+滤泡辅助 T 细胞之间相互作用的遗传中断导致致命的全身性红斑狼疮样自身免疫性疾病的发展。这些发现定义了一种被编程以抑制而不是激活免疫的 CD8 T 细胞亚群，它代表了免疫反应的一个重要调节元件和自身耐受的保证。
