Department of Medicine, Division of Diabetes; Department of Pathology
Animals; Cell Communication; Cells, Cultured; Culture Media, Conditioned; Cytokines; Dendritic Cells; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Interleukin-1; *Lymphocyte Activation; Lymphocyte Culture Test, Mixed; Macrophages; Male; Mice; Rats; Rats, Inbred BB; Rats, Inbred WF; Recombinant Proteins; Species Specificity; Spleen; T-Lymphocytes; Thymidine
Endocrinology, Diabetes, and Metabolism | Medical Pathology | Pathology
Dendritic cells (DC) present antigen and initiate T cell-mediated immune responses. To investigate the possible association of autoimmunity with DC function, we compared the accessory activity of splenic DC from Wistar/Furth (WF) and diabetes-prone (DP) BioBreeding (BB) rats. The latter develop autoimmune diabetes and thyroiditis. DC function was quantified in vitro by measuring T cell proliferation in mitogen-stimulated 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 macrophages, DC from DP rats consistently displayed greater accessory activity. This finding could not be explained by morphological or phenotypic differences between DP and WF DC. In accessory activity assays performed 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 cultured 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 studies 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 hematopoietic 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 activity than are WF DC; and (c) the mechanism responsible for this phenomenon involves differential responsiveness of DP and WF DC to macrophage-derived factors such as IL-1 and GM-CSF.
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Citation: J Clin Invest. 1993 May;91(5):2040-8. Link to article on publisher's site
DOI of Published Version
The Journal of clinical investigation
Tafuri, Anna; Bowers, William E.; Handler, Eugene S.; Appel, Michael C.; Lew, Robert A.; Greiner, Dale L.; Mordes, John P.; and Rossini, Aldo A., "High stimulatory activity of dendritic cells from diabetes-prone BioBreeding/Worcester rats exposed to macrophage-derived factors" (1993). Open Access Articles. 1004.