HIGH STIMULATORY ACTIVITY OF DENDRITIC CELLS FROM DIABETES-PRONE BIOBREEDING WORCESTER RATS EXPOSED TO MACROPHAGE-DERIVED FACTORS

Dendritic cells (DC) present antigen and initiate T cell-mediated immu ne responses. To investigate the possible association of autoimmunity with DC function, we compared the accessory activity of splenic DC fro m Wistar/Furth (WF) and diabetes-prone (DP) BioBreeding (BB) rats. The latter develop autoimmune diabetes and thyroiditis. DC function was q uantified in vitro by measuring T cell proliferation in mitogen-stimul ated and mixed lymphocyte reactions. When purified without macrophage coculture, WF and DP DC displayed similar levels of accessory activity . In contrast, when purified by a method involving coculture with macr ophages, DC from DP rats consistently displayed greater accessory acti vity. This finding could not be explained by morphological or phenotyp ic differences between DP and WF DC. In accessory activity assays perf ormed after reciprocal DC cocultures with DP and WF macrophages, DP DC exhibited higher accessory activity irrespective of macrophage donor strain. We also compared the accessory activity of WF and DP DC cultur ed in the presence of conditioned medium and a mixture of IL-1 and GM- CSF. In all assays, DP DC exhibited higher accessory activity. In stud ies of (WF X DP) F1 hybrids, the high accessory activity of DP DC was observed to be heritable, and studies of WF and DP radiation chimeras indicated that the effect was an intrinsic property of the DP hematopo ietic system. We conclude: (a) splenic DC from DP and WF rats possess similar basal levels of accessory potency; (b) after interaction with macrophages, DC of DP origin are capable of greater stimulatory activi ty than are WF DC; and (c) the mechanism responsible for this phenomen on involves differential responsiveness of DP and WF DC to macrophage- derived factors such as IL-1 and GM CSF.