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

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Presentation Time: 03:15 PM - 04:30 PM
Poster Board Number: B572
Abstract ID: 4897

Presenting Author:
Danielle Kish , Program Manager at Lerner Res. Inst., Cleveland Clin.

Abstract:

Contact hypersensitivity (CHS) is a CD8 cell mediated response to hapten skin sensitization and challenge. Hapten-primed CD8 cell infiltration into the skin challenge site during elicitation of CHS requires infiltration of a novel population of Gr-1⁺ CXCR2⁺ cells that express FasL and perforin. The goal of the current studies was to further characterize these myeloid-derived cells and to determine mechanisms generating the cells in the bone marrow during elicitation of CHS. The cells were purified from the bone marrow of hapten sensitized mice 2 hrs after hapten challenge by depletion of CD3⁺, B220⁺, NK1⁺, F4/80⁺, and class II MHC⁺ cells. Flow cytometry analyses indicate >90% of the remaining bone marrow cells were CD11c⁺, Ly6C⁺, CCR2⁺, expressing FasL⁺ and perforin.  This cell population was at low numbers in the bone marrow of naïve mice but increased to peak numbers 2 hrs. after hapten challenge of sensitized WT and Rag^-/- mice as well as T-cell depleted WT. Generation of these cells was absent in hapten sensitized and challenged TLR4-/- mice. Currently, we are using spectral flow cytometry  to focus on sensitization induced differences in hematopoietic progenitor cell populations in the bone marrow of  TLR4^-/- compared to WT mice. These results indicate that generation of bone marrow-derived Ly6C⁺ CXCR2⁺ FasL⁺ cells in response to inflammation requires TLR4 signaling that occurs independently of T cell activation.