Soluble IL-2Rα facilitates IL-2-mediated immune responses and predicts reduced survival in follicular B-cell non-Hodgkin lymphoma

Abstract

Elevated serum levels of the soluble form of IL-2 receptor α (sIL-2Rα) 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-2Rαlevels were elevated compared with controls and that elevated sIL-2Rα levels before treatment were associated with a poor outcome. To explore the mechanism by which sIL-2Rα may contribute to a poor prognosis in FL, we determined the effects of sIL-2Rα on IL-2 signaling and found that the sIL-2Rα-IL-2 complex promoted T-cell differentiation toward to inhibitory Treg cells rather than T H1 or TH17 cells. Shed by activated T cells that express membrane-bound IL-2Rα, sIL-2Rαfurther 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-2Rα-IL-2 complex, but not with sIL-2Rα alone, inhibited the function of CD8+ T cells. Taken together, these results indicate that sIL-2Rα 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. © 2011 by The American Society of Hematology.