ENDOTOXIN-MEDIATED DENDRITIC CELL RELEASE FROM THE INTESTINE - CHARACTERIZATION OF RELEASED DENDRITIC CELLS AND TNF DEPENDENCE

Dendritic cells (DC) acquire Ag in peripheral tissues and transport it to lymph nodes where they efficiently activate resting T cells. We ha ve shown that i.v. endotoxin causes increased release of intestinal DC into lymph. In this paper we further characterize the release of DC a nd the properties of the released cells. A total of 50 mu g of endotox in injected i.v. causes an increase in DC output within 6 h that peaks between 12 and 24 h, with a maximum output of 8 to 15 times normal. A t the same time lymphocyte output is markedly decreased. The increased output of DC is followed by a decrease to subnormal levels. The stimu lated release of DC is almost totally blocked by a monoclonal anti-TNF -alpha Ab. A second injection of TNF-alpha does not result in further DC release. DC are not released from lymph nodes into efferent lymph b y endotoxin. DC collected from lymph after endotoxin treatment show in creased expression of the p55 IL-2 receptor and the OX48 Ag but otherw ise resemble normal lymph DC. In functional assays they show no signif icant differences from normal in their ability to stimulate a MLR or t o present Ags to sensitized T cells. Immunocytochemistry with the use of MRC OX62 suggests that the DC are released into lymph from the lami na propria of the small intestine. The stimulated release of DC mediat ed by TNF-alpha may be important in regulating Ag presentation in lymp h nodes draining inflammatory sites.