Normal regulatory alpha/beta T cells effectively eliminate abnormally activated T cells lacking the interleukin 2 receptor beta in vivo.
Normal regulatory alpha/beta T cells effectively eliminate abnormally activated T cells lacking the interleukin 2 receptor beta in vivo.
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DOI：
10.1084/jem.190.11.1561
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发表时间：
1999-12-06
影响因子：
15.3
通讯作者：
Nakashima, I
中科院分区：
文献类型：
--
作者：
Suzuki, H;Zhou, Y W;Kato, M;Mak, T W;Nakashima, I
虽然白细胞介素2（IL-2）被认为是T细胞生长的最重要的细胞因子，但缺乏IL-2或其受体分子的组分的动物具有更多扩增的具有活化记忆表型的T细胞，这表明IL-2/IL-2受体系统在调节T细胞群体的大小和活性中起不可或缺的作用。在本研究中，我们使用骨髓移植和T细胞转移系统研究了IL-2受体β链（IL-2 R β）−/−小鼠中活化T细胞异常扩增的可能机制。在这里，我们发现，在用IL-2 R β2/−和IL-2 R β1/+骨髓细胞的混合物重建的小鼠中，IL-2 R β2/− T细胞没有发展到异常活化的阶段，并且当两种细胞共同转移到T细胞缺陷型宿主小鼠时，已经活化的IL-2 R β 2/− T细胞被IL-2 R β1/+ T细胞有效地清除。这种调节和/或消除依赖于携带α/β型T细胞受体的T细胞，尤其是CD 8 + T细胞，而不依赖于Fas-Fas配体（FasL）系统。清除活化IL-2 R β2/− T细胞的IL-2 R β1/+ T细胞表达FasL、穿孔素、颗粒酶B和肿瘤坏死因子α/β。这些结果表明IL-2 R β的一种新功能，其对于诱导起消除活化T细胞作用的调节性T细胞是必需的。
Although interleukin 2 (IL-2) has been thought to be the most important cytokine for T cell growth, animals lacking IL-2 or a component of its receptor molecules have more expanded T cells with activated memory phenotype, indicating an indispensable role for the IL-2/IL-2 receptor system in regulating the size and activity of the T cell population. In this study, we investigated the possible mechanism of abnormal expansion of activated T cells in IL-2 receptor β chain (IL-2Rβ)−/− mice using the systems of bone marrow transplantation and T cell transfer. Here, we show that IL-2Rβ2/− T cells in mice reconstituted with a mixture of IL-2Rβ2/− and IL-2Rβ1/+ bone marrow cells did not develop into an abnormally activated stage, and that already activated IL-2Rβ2/− T cells were effectively eliminated by IL-2Rβ1/+ T cells when both cells were cotransferred to T cell–deficient host mice. This regulation and/or elimination was dependent on T cells bearing α/β type T cell receptor, especially on CD8+ T cells and independent of the Fas–Fas ligand (FasL) system. IL-2Rβ1/+ T cells that eliminated activated IL-2Rβ2/− T cells expressed FasL, perforin, granzyme B, and tumor necrosis factor α/β. These results indicate a novel function of IL-2Rβ that is necessary for the induction of regulatory T cells acting to eliminate activated T cells.