OX40-mediated differentiation to effector function requires IL-2 receptor signaling but not CD28, CD40, IL-12Rβ2, or T-bet

Cortny A. Williams, Susan Murray, Andrew D. Weinberg, David Parker

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Ag-specific CD4 T cells transferred into unirradiated Ag-bearing recipients proliferate, but survival and accumulation of proliferating cell is not extensive and the donor cells do not that acquire effector functions. We previously showed that a single costimulatory signal delivered by an agonist Ab to OX40 (CD134) promotes accumulation of proliferating cells and promotes differentiation to effector CD4 T cells capable of secreting IFN-γ. In this study, we determined whether OX40 costimulation requires supporting costimulatory or differentiation signals to drive acquisition of effector T cell function. We report that OX40 engagement drives effector T cell differentiation in the absence of CD28 and CD40 signals. Two important regulators of Th1 differentiation, IL-12R and T-bet, also are not required for acquisition of effector function in CD4 T cells responsive to OX40 stimulation. Finally, we show that CD25-deficient CD4 T cells produce little IFN-γ in the presence of OX40 costimulation compared with wild type, suggesting that IL-2R signalling is required for efficient OX40-mediated differentiation to IFN-γ secretion.

Original languageEnglish (US)
Pages (from-to)7694-7702
Number of pages9
JournalJournal of Immunology
Volume178
Issue number12
StatePublished - Jun 15 2007

Fingerprint

Interleukin-2 Receptors
T-Lymphocytes
Cell Differentiation

ASJC Scopus subject areas

  • Immunology

Cite this

OX40-mediated differentiation to effector function requires IL-2 receptor signaling but not CD28, CD40, IL-12Rβ2, or T-bet. / Williams, Cortny A.; Murray, Susan; Weinberg, Andrew D.; Parker, David.

In: Journal of Immunology, Vol. 178, No. 12, 15.06.2007, p. 7694-7702.

Research output: Contribution to journalArticle

Williams, Cortny A. ; Murray, Susan ; Weinberg, Andrew D. ; Parker, David. / OX40-mediated differentiation to effector function requires IL-2 receptor signaling but not CD28, CD40, IL-12Rβ2, or T-bet. In: Journal of Immunology. 2007 ; Vol. 178, No. 12. pp. 7694-7702.
@article{020caa84c0984275aaed4386f450f826,
title = "OX40-mediated differentiation to effector function requires IL-2 receptor signaling but not CD28, CD40, IL-12Rβ2, or T-bet",
abstract = "Ag-specific CD4 T cells transferred into unirradiated Ag-bearing recipients proliferate, but survival and accumulation of proliferating cell is not extensive and the donor cells do not that acquire effector functions. We previously showed that a single costimulatory signal delivered by an agonist Ab to OX40 (CD134) promotes accumulation of proliferating cells and promotes differentiation to effector CD4 T cells capable of secreting IFN-γ. In this study, we determined whether OX40 costimulation requires supporting costimulatory or differentiation signals to drive acquisition of effector T cell function. We report that OX40 engagement drives effector T cell differentiation in the absence of CD28 and CD40 signals. Two important regulators of Th1 differentiation, IL-12R and T-bet, also are not required for acquisition of effector function in CD4 T cells responsive to OX40 stimulation. Finally, we show that CD25-deficient CD4 T cells produce little IFN-γ in the presence of OX40 costimulation compared with wild type, suggesting that IL-2R signalling is required for efficient OX40-mediated differentiation to IFN-γ secretion.",
author = "Williams, {Cortny A.} and Susan Murray and Weinberg, {Andrew D.} and David Parker",
year = "2007",
month = "6",
day = "15",
language = "English (US)",
volume = "178",
pages = "7694--7702",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "12",

}

TY - JOUR

T1 - OX40-mediated differentiation to effector function requires IL-2 receptor signaling but not CD28, CD40, IL-12Rβ2, or T-bet

AU - Williams, Cortny A.

AU - Murray, Susan

AU - Weinberg, Andrew D.

AU - Parker, David

PY - 2007/6/15

Y1 - 2007/6/15

N2 - Ag-specific CD4 T cells transferred into unirradiated Ag-bearing recipients proliferate, but survival and accumulation of proliferating cell is not extensive and the donor cells do not that acquire effector functions. We previously showed that a single costimulatory signal delivered by an agonist Ab to OX40 (CD134) promotes accumulation of proliferating cells and promotes differentiation to effector CD4 T cells capable of secreting IFN-γ. In this study, we determined whether OX40 costimulation requires supporting costimulatory or differentiation signals to drive acquisition of effector T cell function. We report that OX40 engagement drives effector T cell differentiation in the absence of CD28 and CD40 signals. Two important regulators of Th1 differentiation, IL-12R and T-bet, also are not required for acquisition of effector function in CD4 T cells responsive to OX40 stimulation. Finally, we show that CD25-deficient CD4 T cells produce little IFN-γ in the presence of OX40 costimulation compared with wild type, suggesting that IL-2R signalling is required for efficient OX40-mediated differentiation to IFN-γ secretion.

AB - Ag-specific CD4 T cells transferred into unirradiated Ag-bearing recipients proliferate, but survival and accumulation of proliferating cell is not extensive and the donor cells do not that acquire effector functions. We previously showed that a single costimulatory signal delivered by an agonist Ab to OX40 (CD134) promotes accumulation of proliferating cells and promotes differentiation to effector CD4 T cells capable of secreting IFN-γ. In this study, we determined whether OX40 costimulation requires supporting costimulatory or differentiation signals to drive acquisition of effector T cell function. We report that OX40 engagement drives effector T cell differentiation in the absence of CD28 and CD40 signals. Two important regulators of Th1 differentiation, IL-12R and T-bet, also are not required for acquisition of effector function in CD4 T cells responsive to OX40 stimulation. Finally, we show that CD25-deficient CD4 T cells produce little IFN-γ in the presence of OX40 costimulation compared with wild type, suggesting that IL-2R signalling is required for efficient OX40-mediated differentiation to IFN-γ secretion.

UR - http://www.scopus.com/inward/record.url?scp=34250180851&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34250180851&partnerID=8YFLogxK

M3 - Article

C2 - 17548606

AN - SCOPUS:34250180851

VL - 178

SP - 7694

EP - 7702

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 12

ER -