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 language | English (US) |
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Pages (from-to) | 1635-1644 |
Number of pages | 10 |
Journal | Journal of Immunology |
Volume | 178 |
Issue number | 3 |
DOIs | |
State | Published - Feb 1 2007 |
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology