Tafuri A, Bowers W E, Handler E S, Appel M, Lew R, Greiner D, Mordes J P, Rossini A A
Department of Medicine, University of Massachusetts Medical School, Worcester 01655.
J Clin Invest. 1993 May;91(5):2040-8. doi: 10.1172/JCI116426.
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.
树突状细胞（DC）呈递抗原并启动T细胞介导的免疫反应。为了研究自身免疫与DC功能之间可能存在的关联，我们比较了Wistar/Furth（WF）大鼠和易患糖尿病（DP）的BioBreeding（BB）大鼠脾脏DC的辅助活性。后者会发生自身免疫性糖尿病和甲状腺炎。通过在有丝分裂原刺激的混合淋巴细胞反应中测量T细胞增殖，在体外对DC功能进行定量。当在没有巨噬细胞共培养的情况下纯化时，WF和DP DC显示出相似水平的辅助活性。相比之下，当通过与巨噬细胞共培养的方法纯化时，DP大鼠的DC始终表现出更高的辅助活性。这一发现无法用DP和WF DC之间的形态学或表型差异来解释。在用DP和WF巨噬细胞进行相互DC共培养后进行的辅助活性测定中，无论巨噬细胞供体品系如何，DP DC都表现出更高的辅助活性。我们还比较了在条件培养基以及IL-1和GM-CSF混合物存在下培养的WF和DP DC的辅助活性。在所有测定中，DP DC都表现出更高的辅助活性。在对（WF×DP）F1杂种的研究中，观察到DP DC的高辅助活性是可遗传的，对WF和DP辐射嵌合体的研究表明，这种效应是DP造血系统的固有特性。我们得出以下结论：（a）DP和WF大鼠的脾脏DC具有相似的基础辅助能力水平；（b）与巨噬细胞相互作用后，源自DP的DC比WF DC具有更强的刺激活性；（c）导致这种现象的机制涉及DP和WF DC对巨噬细胞衍生因子（如IL-1和GM-CSF）的不同反应性。
