Induction of granzyme B and T cell cytotoxic capacity by IL-2 or IL-15 without antigens: Multiclonal responses that are extremely lytic if triggered and short-lived after cytokine withdrawal
Induction of granzyme B and T cell cytotoxic capacity by IL-2 or IL-15 without antigens: Multiclonal responses that are extremely lytic if triggered and short-lived after cytokine withdrawal
复制标题
DOI：
10.1016/j.cyto.2006.11.008
复制
发表时间：
2006-11-01
期刊：
影响因子：
3.8
通讯作者：
Hudig, Dorothy
中科院分区：
文献类型：
--
作者：
Tamang, David L.;Redelman, Doug;Hudig, Dorothy
这些研究的目的是确定诱导颗粒酶 B、细胞毒性颗粒和穿孔素依赖性裂解能力的最低要求。令我们惊讶的是，在没有抗原或 TCR 刺激的情况下，IL-2 和 IL-15 不仅诱导增殖，而且还诱导 CD8+ T 细胞产生深刻的颗粒酶 B 和裂解能力。将小鼠脾细胞与小鼠 r-IL-2 或 r-IL-15 一起孵育三天，通过抗 CD3 重定向裂解进行测试，并检查细胞内颗粒酶 B 和 T 细胞活化标记。使用 10(-8) M IL-2 或 IL-15，在效应子与靶标比例为 1:1 的情况下，野生型 T 细胞（而非穿孔素基因消除小鼠）介导的 T 细胞具有出色的裂解活性，这与多克隆激活一致。较低的白细胞介素浓度诱导较低的裂解活性。通过流式细胞术检测到，在第 0 天检测不到颗粒酶 B，并在第 3 天在 CD44(hi) CD8+ T 细胞中显着升高。单独使用细胞因子时，颗粒酶 B 的升高程度与刀豆球蛋白 A 与细胞因子组合时的升高程度一样高。一些离体CD8+T细胞是CD122+，培养的颗粒酶B+细胞也是如此，因此这两个细胞群都对白细胞介素具有低亲和力受体。 CFSE 标记检测到只有部分活化细胞在增殖。当细胞因子被撤除后，细胞在 24 小时内失去裂解活性，然后在接下来的 24 小时内死亡。我们的结果表明，高浓度的 IL-2 或 IL-15 将激活许多 T 细胞的裂解能力和颗粒酶 B 表达，并且不需要抗原识别。 (c) 2006 Elsevier Ltd. 保留所有权利。
The purpose of these studies was to determine the minimal requirements to induce granzyme B, cytotoxic granules and perforin-dependent lytic capacity. To our surprise, both IL-2 and IL-15 induced not only proliferation, but also profound granzyme B and lytic capacity from CD8+ T cells in the absence of antigen or TCR-stimulation. Mouse splenocytes were incubated with mouse r-IL-2 or r-IL-15 for three days, tested by anti-CD3 redirected lysis and examined for intracellular granzyme B and for T cell activation markers. With 10(-8) M IL-2 or IL-15, there was excellent lytic activity at 1:1 effector to target ratios mediated by T cells from wild-type but not from perforin-gene-ablated mice, consistent with multiclonal activation. Lower interleukin concentrations induced less lytic activity. Granzyme B was undetectable on day 0, and greatly elevated on day 3 in CD44(hi) CD8+ T cells as detected by flow cytometry. Cytokines alone elevated the granzyme B as much as concanavalin A combined with the cytokines. Some ex vivo CD8(+) T cells were CD122(+), as were the cultured granzyme B+ cells, thus both populations had low-affinity receptors for the interleukins. Only some of the activated cells were proliferating as detected by CFSE labeling. When the cytokines were withdrawn, the cells lost lytic activity within 24 h and then within the next 24 h, died. Our results suggest that high concentrations of either IL-2 or IL-15 will activate the lytic capacity and granzyme B expression of many T cells and that antigen recognition is not required. (c) 2006 Elsevier Ltd. All rights reserved.