Wang R, Murphy K M, Loh D Y, Weaver C, Russell J H
Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, MO 63110.
J Immunol. 1993 May 1;150(9):3832-42.
Stimulation of the TCR of activated, mature T cells by an APC produces a spectrum of functional responses. Most of those responses positively promote immunity and inflammation. However, death of the responding T cell, which would limit subsequent inflammation, can also result from such stimulation. We compare the Ag threshold necessary to promote inflammation through cytokine production with the Ag threshold necessary to limit inflammation through T cell death. These two responses are independently regulated by the APC and this regulation is selective for both different APC products and different T cell subsets. The costimulator B7 selectively decreases the Ag threshold for cytokine production in Th1 cells with no effect on the Ag threshold for Th1 death. B7 has no effect on the Th2 Ag threshold for cytokine production or death. In contrast, IFN-gamma negatively modulates a macrophage product that selectively increases the threshold of Ag necessary to stimulate death in Th2 cells, but has no effect on cytokine production by Th2 cells or cytokine production or death of Th1 cells. This selective regulation of cytokine production and T cell death may play an important role in both shaping the quality of a given immune response and in providing a general mechanism for the regulation of the immune response by limiting inflammation and through peripheral deletion of inappropriate T cell specificities.
抗原呈递细胞（APC）刺激活化的成熟T细胞的TCR会产生一系列功能反应。这些反应大多能积极促进免疫和炎症。然而，这种刺激也可能导致反应性T细胞死亡，这会限制后续的炎症反应。我们比较了通过细胞因子产生促进炎症所需的抗原阈值与通过T细胞死亡限制炎症所需的抗原阈值。这两种反应由APC独立调节，并且这种调节对不同的APC产物和不同的T细胞亚群具有选择性。共刺激分子B7选择性降低Th1细胞中细胞因子产生的抗原阈值，而对Th1细胞死亡的抗原阈值没有影响。B7对Th2细胞因子产生或死亡的抗原阈值没有影响。相反，干扰素-γ负向调节一种巨噬细胞产物，该产物选择性增加刺激Th2细胞死亡所需的抗原阈值，但对Th2细胞的细胞因子产生或Th1细胞的细胞因子产生及死亡没有影响。细胞因子产生和T细胞死亡的这种选择性调节可能在塑造特定免疫反应的质量以及通过限制炎症和外周清除不适当的T细胞特异性来提供免疫反应调节的一般机制方面发挥重要作用。
