TLR4 dependent generation of a novel bone marrow-derived inflammatory monocyte population required for elicitation of skin contact hypersensitivity responses

Abstract Contact hypersensitivity (CHS) is a CD8 T cell mediated response to hapten skin sensitization and challenge. Hapten-primed infiltration into the challenge site during elicitation of CHS requires prior activation novel population Gr-1 +CXCR2 +cells expressing FasL perforin. The goal these studies was further characterize this myeloid-derived cells determine mechanisms generating in bone marrow CHS. myeloid were purified from sensitized mice 2 hrs after by depletion CD3 +, B220 NK1 F4/80 class II MHC +and Ly6G +cells. Flow cytometry analyses indicate >90% remaining CD11c Ly6C CCR2 This at low numbers naïve but increased peak hrs. WT Rag −/−mice T-cell depleted mice. Generation absent challenged TLR4-deficient inhibited treatment with anti-TNFa mAb time Whereas generation neutrophils anti-G-CSF antibody, following These results that marrow-derived perforin inflammation TNFa TLR4 signaling occurs independently activation.