Soluble IL-2Rα facilitates IL-2-mediated immune responses and predicts reduced survival in follicular B-cell non-Hodgkin lymphoma
Soluble IL-2Rα facilitates IL-2-mediated immune responses and predicts reduced survival in follicular B-cell non-Hodgkin lymphoma
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DOI：
10.1182/blood-2011-03-340885
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发表时间：
2011-09-08
期刊：
影响因子：
20.3
通讯作者：
Ansell, Stephen M.
中科院分区：
文献类型：
--
作者：
Yang, Zhi-Zhang;Grote, Deanna M.;Ansell, Stephen M.
在各种不同类型的癌症中，血清可溶性白介素2受体α(sIL-2Rα)水平升高与预后不良相关。然而，它的生物学相关性仍然不清楚，也存在争议。在滤泡性B细胞性非霍奇金淋巴瘤(FL)患者中，我们观察到血清sIL-2Rα水平较对照组升高，且治疗前sIL-2Rα水平升高与预后不良有关。为了探讨sIL-2Rα可能导致FL预后不良的机制，我们检测了sIL-2Rα对IL-2信号转导的影响，发现sIL-2Rα-IL-2复合体促进T细胞分化为抑制T-reg细胞，而不是T(H)1或T(H)17细胞。通过表达膜结合IL-2Rα的活化T细胞，sIL-2Rα进一步增强了IL-2介导的Stat5的磷酸化，从而显著上调了CD4(+)T细胞中Foxp3的表达。我们发现，用IL-2或sIL-2Rα-IL-2复合体处理CD4(+)T细胞，但不单独用sIL-2Rα处理，可抑制CD8(+)T细胞的功能。综上所述，这些结果表明sIL-2Rα通过结合IL-2和促进IL-2信号转导而不是耗尽IL-2和阻断其功能而在FL中发挥积极的生物学作用。(血。2011；118(10)：2809-2820)
Elevated serum levels of the soluble form of IL-2 receptor alpha (sIL-2R alpha) have been correlated with a poor prognosis in a variety of different types of cancers. However, its biologic relevance remains unclear and controversial. In patients with follicular B-cell non-Hodgkin lymphoma (FL), we observed that serum sIL-2R alpha levels were elevated compared with controls and that elevated sIL-2R alpha levels before treatment were associated with a poor outcome. To explore the mechanism by which sIL-2R alpha may contribute to a poor prognosis in FL, we determined the effects of sIL-2R alpha on IL-2 signaling and found that the sIL-2R alpha-IL-2 complex promoted T-cell differentiation toward to inhibitory T-reg cells rather than T(H)1 or T(H)17 cells. Shed by activated T cells that express membrane-bound IL-2R alpha, sIL-2R alpha further enhanced IL-2-mediated phosphorylation of Stat5 thereby significantly up-regulating Foxp3 expression in CD4(+) T cells. We found that CD4(+) T cells treated with either IL-2 or sIL-2R alpha-IL-2 complex, but not with sIL-2R alpha alone, inhibited the function of CD8(+) T cells. Taken together, these results indicate that sIL-2R alpha actually plays an active biologic role in FL by binding IL-2 and promoting IL-2 signaling rather than depleting IL-2 and blocking its function. (Blood. 2011; 118(10): 2809-2820)