Vasquez A C, Feili-Hariri M, Tan R J, Morel P A
Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Clin Exp Immunol. 2004 Feb;135(2):209-18. doi: 10.1111/j.1365-2249.2003.02359.x.
The phenotype and function of splenic DC populations from diabetes-prone NOD mice were characterized and compared to DC from diabetes-resistant strains in the presence or absence of Flt3 ligand (FL) treatment. NOD mice were found to have significantly fewer CD8alpha+ DC than both B10.BR and C57BL/6 mice, and this defect was reversed by FL treatment. Freshly isolated CD8alpha+ and CD8alpha- DC from all three strains were found to express similar levels of costimulatory molecules and this was similar in both FL-treated and untreated animals. IL-12 p40 production was significantly lower in purified CD11c+ DC from NOD mice compared to DC from C57BL/6 or B10.BR mice. CD8alpha+ DC isolated from NOD mice produced lower levels of IL-12p40 than CD8alpha+ DC from C57CBL/6 and this was dependent on the nature of the stimulus given. In contrast both CD8alpha+ and CD8alpha- DC from FL-treated mice produced high levels of IL-12p40 following activation, but only the CD8alpha- DC produced IL-12p70. Functionally, freshly isolated CD8alpha- DC were more stimulatory than CD8alpha+ DC in a primary allogeneic mixed lymphocyte reaction. However, DC maturation resulted in increased T cell stimulatory capacity for both DC subsets, and this pattern was seen in all strains. These results demonstrate significant differences in phenotype and function of splenic NOD CD8alpha+ DC, and further suggest that FL treatment may reverse some of these abnormalities.
对易患糖尿病的非肥胖糖尿病（NOD）小鼠脾脏树突状细胞（DC）群体的表型和功能进行了表征，并在有或没有Flt3配体（FL）处理的情况下，将其与抗糖尿病品系的DC进行了比较。发现NOD小鼠的CD8α⁺ DC明显少于B10.BR和C57BL/6小鼠，并且这种缺陷通过FL处理得以逆转。发现来自所有三个品系的新鲜分离的CD8α⁺和CD8α⁻ DC表达相似水平的共刺激分子，并且在FL处理和未处理的动物中都是如此。与来自C57BL/6或B10.BR小鼠的DC相比，NOD小鼠纯化的CD11c⁺ DC中IL-12 p40的产生明显更低。从NOD小鼠分离的CD8α⁺ DC产生的IL-12p40水平低于来自C57CBL/6的CD8α⁺ DC，这取决于所给予刺激的性质。相反，来自FL处理小鼠的CD8α⁺和CD8α⁻ DC在激活后均产生高水平的IL-12p40，但只有CD8α⁻ DC产生IL-12p70。在功能上，在初次同种异体混合淋巴细胞反应中，新鲜分离的CD8α⁻ DC比CD8α⁺ DC更具刺激性。然而，DC成熟导致两个DC亚群的T细胞刺激能力增加，并且这种模式在所有品系中都可见。这些结果证明了脾脏NOD CD8α⁺ DC在表型和功能上的显著差异，并进一步表明FL处理可能会逆转其中一些异常情况。
