Abstract
Abstract Dendritic cells (DCs) induce immunity or tolerance depending on the presence of danger signals. LPS is a danger signal with multiple effects on DCs, besides activation. Unpublished results from our lab show that LPS induces DC death in vitro and in vivo. It has also been reported that DCs treated with LPS during their development remained immature and induced T cell anergy. LPS triggers TLR4, a PRR also stimulated by endogenous danger signals, like HMGB1, released during tissue damage. We used a mouse transplant model to determine the effects of simultaneous exposure to LPS and endogenous danger signals, released during engraftment, on DC functions and graft survival. We used the single minor male-specific H-Y antigen mismatch. We transplanted skin of male C57BL/6 mice onto syngeneic female recipients. We administered 4 i.p. injections of 12.5ug/mouse of LPS or PBS every other day. Control mice rejected male skin graft in 24-34 days, as expected, while mice treated with LPS did not reject the graft until 64 days or later. Studying the DCs migrating out of the graft, we found a sharp decrease of DCs 48 hours post transplant and the DC loss was more severe after LPS. LPS also decreased the number of DCs with high surface expression of MHC class II. These findings suggest that the combination of endogenous danger signals released during engraftment and LPS are either killing the DCs or preventing them from maturing thus allowing for tolerance of the male skin graft.
Published Version
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