Division of Hematology, Department of Internal Medicine, Geneva University Hospitals and University of Geneva, Geneva, Switzerland.
Eur J Immunol. 2010 Nov;40(11):3246-54. doi: 10.1002/eji.200940016. Epub 2010 Oct 19.
We studied early NK-cell recovery in 29 allografted patients undergoing different lymphoreductive regimens. Already at 2 wk after graft take, the number of NK cells had reached (supra)normal levels but NK-cell subsets were skewed. The number of CD56(dim) CD16(bright) NK cells was low and correlated strongly with the level of hematopoiesis, whereas the number of the more abundant NK cells expressing high levels of CD56 did not. Post-transplant CD56(bright) NK cells (ptCD56(bright)) differed from CD56(bright) NK cells in normal controls (CD56(bright)) in being HLA-DR- and perforin-positive, CCR7(-), CD27(-), CD127(-) and mostly c-kit(-). CD56(bright) from normal controls stimulated by IL-15 in vitro (NK(IL-15)) acquired all the characteristics distinguishing CD56(bright) from ptCD56(bright). IL-2 exerted similar effects. Moreover, when cultured without cytokines, ptCD56(bright), CD56(bright) and NK(IL-15) responded similarly by upregulating CD127 and c-kit but not CCR7. IL-12 stimulated IFN-γ production in ptCD56(bright), whereas CD56(bright) responded only to IL-12 plus IL-15. Hence, ptCD56(bright) have all the features of cytokine-stimulated CD56(bright). Because only patients with low numbers of T cells had high numbers of ptCD56(bright), we conclude that ptCD56(bright) are activated CD56(bright) that expand while competing with T cells for the elevated post-transplant level of IL-15.
我们研究了 29 名接受不同淋巴耗竭方案同种异体移植患者的早期 NK 细胞恢复情况。在移植物接受后 2 周，NK 细胞数量已达到（超）正常水平，但 NK 细胞亚群出现偏倚。CD56(dim) CD16(bright) NK 细胞数量较低，与造血水平密切相关，而表达高水平 CD56 的更丰富 NK 细胞数量则没有。移植后 CD56(bright) NK 细胞（ptCD56(bright)）与正常对照（CD56(bright)）中的 CD56(bright) NK 细胞不同，表现为 HLA-DR 和穿孔素阳性、CCR7(-)、CD27(-)、CD127(-)和大部分 c-kit(-)。体外经 IL-15 刺激的正常对照 CD56(bright)（NK(IL-15)）获得了区分 CD56(bright)和 ptCD56(bright)的所有特征。IL-2 也产生类似的作用。此外，当在无细胞因子的情况下培养时，ptCD56(bright)、CD56(bright)和 NK(IL-15)通过上调 CD127 和 c-kit 但不上调 CCR7 而做出类似的反应。IL-12 刺激 ptCD56(bright)产生 IFN-γ，而 CD56(bright)仅对 IL-12 加 IL-15 有反应。因此，ptCD56(bright)具有受细胞因子刺激的 CD56(bright)的所有特征。由于只有 T 细胞数量低的患者具有高数量的 ptCD56(bright)，我们得出结论，ptCD56(bright)是激活的 CD56(bright)，在与 T 细胞竞争移植后升高的 IL-15 水平时会扩增。
