Suppression of early IL-4 production underlies the failure of CD4 T cells activated by TLR-stimulated dendritic cells to differentiate into Th2 cells

Jie Sun, Edward J. Pearce

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Dendritic cells (DCs) activated through TLRs provide a potent negative signal for Th2 cell development that is independent of positive signals for Th1 cell development such as IL-12 and IFN-γ. In this study we demonstrate that the ability of TLR-activated DCs to suppress Th2 cell development is Ag dose-independent and unique to DCs that have been activated through TLRs vs by cytokines. We show that TLR-activated DCs inhibit early IL-4 production by CD4 T cells and thus inhibit their ability to subsequently increase GATA-3 expression and commit to the Th2 lineage. This occurs independently of expression of the GATA-3 antagonist T-bet. Although CD4 T cells activated by TLR-activated DCs make IL-2, they are not capable of phosphorylating STAT5 in response to this cytokine. This inhibition of responsiveness to IL-2 appears to underlie the failure to make early IL-4. Our findings suggest that DCs provide instructional signals for T cell differentiation before cytoldne-mediated Th cell selection and outgrowth.

Original languageEnglish (US)
Pages (from-to)1635-1644
Number of pages10
JournalJournal of Immunology
Volume178
Issue number3
DOIs
StatePublished - Feb 1 2007

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Th2 Cells
Interleukin-4
Dendritic Cells
T-Lymphocytes
Interleukin-2
Cytokines
Th1 Cells
Interleukin-12
Cell Differentiation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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Suppression of early IL-4 production underlies the failure of CD4 T cells activated by TLR-stimulated dendritic cells to differentiate into Th2 cells. / Sun, Jie; Pearce, Edward J.

In: Journal of Immunology, Vol. 178, No. 3, 01.02.2007, p. 1635-1644.

Research output: Contribution to journalArticle

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