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

Zhi Zhang Yang, Deanna M. Grote, Steven C. Ziesmer, Michelle K. Manske, Thomas Elmer Witzig, Anne J Novak, Stephen Maxted Ansell

Research output: Contribution to journalArticle

71 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2809-2820
Number of pages12
JournalBlood
Volume118
Issue number10
DOIs
StatePublished - Sep 8 2011

Fingerprint

Interleukin-2 Receptors
B-Cell Lymphoma
Non-Hodgkin's Lymphoma
Interleukin-2
T-cells
Cells
Survival
T-Lymphocytes
Th17 Cells
Phosphorylation
Regulatory T-Lymphocytes
Serum
Cell Differentiation
Cell Membrane
Membranes

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Soluble IL-2Rα facilitates IL-2-mediated immune responses and predicts reduced survival in follicular B-cell non-Hodgkin lymphoma. / Yang, Zhi Zhang; Grote, Deanna M.; Ziesmer, Steven C.; Manske, Michelle K.; Witzig, Thomas Elmer; Novak, Anne J; Ansell, Stephen Maxted.

In: Blood, Vol. 118, No. 10, 08.09.2011, p. 2809-2820.

Research output: Contribution to journalArticle

@article{5bb7543faa094d28832941b7f6ed3900,
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-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.",
author = "Yang, {Zhi Zhang} and Grote, {Deanna M.} and Ziesmer, {Steven C.} and Manske, {Michelle K.} and Witzig, {Thomas Elmer} and Novak, {Anne J} and Ansell, {Stephen Maxted}",
year = "2011",
month = "9",
day = "8",
doi = "10.1182/blood-2011-03-340885",
language = "English (US)",
volume = "118",
pages = "2809--2820",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "10",

}

TY - JOUR

T1 - Soluble IL-2Rα facilitates IL-2-mediated immune responses and predicts reduced survival in follicular B-cell non-Hodgkin lymphoma

AU - Yang, Zhi Zhang

AU - Grote, Deanna M.

AU - Ziesmer, Steven C.

AU - Manske, Michelle K.

AU - Witzig, Thomas Elmer

AU - Novak, Anne J

AU - Ansell, Stephen Maxted

PY - 2011/9/8

Y1 - 2011/9/8

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=80052623454&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80052623454&partnerID=8YFLogxK

U2 - 10.1182/blood-2011-03-340885

DO - 10.1182/blood-2011-03-340885

M3 - Article

C2 - 21719603

AN - SCOPUS:80052623454

VL - 118

SP - 2809

EP - 2820

JO - Blood

JF - Blood

SN - 0006-4971

IS - 10

ER -