title: 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-2Rα levels 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 T(reg) cells rather than T(H)1 or T(H)17 cells. Shed by activated T cells that express membrane-bound IL-2Rα, sIL-2Rα 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-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.
authors: Division of Hematology and Internal Medicine, Mayo Clinic, Rochester, MN 55905, USA. yang.zhizhang@mayo.edu
authors: Zhi-Zhang
authors: ZZ
authors: Yang
authors: Deanna M
authors: DM
authors: Grote
authors: Steven C
authors: SC
authors: Ziesmer
authors: Michelle K
authors: MK
authors: Manske
authors: Thomas E
authors: TE
authors: Witzig
authors: Anne J
authors: AJ
authors: Novak
authors: Stephen M
authors: SM
authors: Ansell
mesh_terms: D015153:Blotting, Western; D016022:Case-Control Studies; D002454:Cell Differentiation; D049109:Cell Proliferation; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D007376:Interleukin-2 / Q000276:immunology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology* / Q000378:metabolism; D016393:Lymphoma, B-Cell / Q000276:immunology* / Q000378:metabolism / Q000401:mortality*; D008224:Lymphoma, Follicular / Q000276:immunology* / Q000378:metabolism / Q000401:mortality*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics; D015375:Receptors, Interleukin-2 / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050799:STAT5 Transcription Factor / Q000378:metabolism; D015996:Survival Rate; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D050799:STAT5 Transcription Factor