Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 204, Issue 7, Pages 1525-1531Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20062305
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Toll-like receptor (TLR) ligation is believed to skew T cell responses toward T helper (Th)1 differentiation by inducing interleukin (Q-12 secretion by CD8(+) dendritic cells (DCs). However, TLR-dependent Th1 responses occur in the absence of IL-12. To determine how DCs induce Th1 differentiation in the absence of IL-12, we examined the response of IL-12-deficient DCs to bacterial li popolysaccha ride (LPS). We find that LIPS activates MyD88-dependent Delta 4 Notch-like ligand expression by CD8- DCs, and that these cells direct Th1 differentiation by an IL-12-independent and Notch-dependent mechanism in vitro and in vivo. Thus, activation of the two DC subsets by TLR4 leads to Th1 responses by two distinct MyD88-dependent pathways.
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