108 INTERLEUKIN 10 SECRETION DIFFERENTIATES BETWEEN INTERSTITIAL DENDRITIC CELLS FROM HUMAN LIVER AND SKIN

S. Goddard, D Adams. Liver Unit Laboratories, Queen Elizabeth Hospital, Birmingham, UK

Dendritic cells are thought to be the only cell capable of initiating primary immune responses, to produce both immunity and tolerance. They are also able to direct the kind of T cell response generated to specific antigen. Liver immune responses are relatively weak, for instance liver allografts are less susceptible to rejection. Human liver dendritic cells (DCs), which may orchestrate the liver's unique immunoregulatory functions, remain poorly characterised. We used a novel technique of overnight migration from tissue pieces of normal liver and skin to obtain human tissue-derived DCs with minimal manipulation and no additional cytokine treatment.

As presented at a previous BSG liver DCs have a monocyte-like morphology and a partially mature phenotype after migration overnight from tissue. We now show that liver DCs express CD123, a marker expressed by a subset of DCs associated with initiating Th2 T cell responses. In addition, a functional comparison was made between liver and skin DCs isolated the same way. ELISA measurement of cytokine in DC conditioned media showed that, liver DCs produced IL-10 whereas skin DCs failed to secrete IL-10 even after stimulation and neither skin nor liver-derived DCs secreted IL-12. The effect of DC stimulation on T cells was studied following coculture and T cell intracellular cytokine staining. Liver DCs stimulated T cells to secrete IL-10 whereas skin DCs stimulated IFNγ and IL-4 secretion in the absence of detectable IL-10.

We show for the first time clear tissue-specific differences in human non-lymphoid DCs. The ability of liver DCs to secrete IL-10, a cytokine implicated in down-regulation of immune responses, may explain how interstitial DCs from normal liver can maintain tolerance to gut derived Ag, by controlling the type of response generated in tissue or draining lymph node

109 SUSCEPTIBILITY TO PRIMARY SCLEROSING CHOLANGITIS IS ASSOCIATED WITH A POLYMORPHISM OF THE MMP-9 (GELATINASE B) GENE

S.N. …