De Smedt T, Butz E, Smith J, Maldonado-López R, Pajak B, Moser M, Maliszewski C
Department of Discovery Research, Immunex Corporation, Seattle, Washington, USA.
J Leukoc Biol. 2001 Jun;69(6):951-8.
Dendritic cells (DCs) are essential for the priming of immune responses. This antigen-presenting function of DCs develops in sequence in a process called maturation, during which they become potent sensitizers of naïve T cells but reduce their ability to capture and process antigens. Some heterogeneity exists in mouse-DC populations, and two distinct subsets of DCs expressing high levels of CD11c can be identified on the basis of CD8alpha expression. We have studied the phenotype and maturation state of mouse splenic CD8alpha(-) and CD8alpha(+) DCs. Both subsets were found to reside in the spleen as immature cells and to undergo a phenotypic maturation upon culture in vitro in GM-CSF-containing medium or in vivo in response to lipopolysaccharide. In vitro and in vivo analyses showed that this maturation process is an absolute requisite for DCs to acquire their T-cell priming capacity, transforming CD8alpha(-) and CD8alpha(+) DCs into potent and equally efficient activators of naïve CD4(+) and CD8(+) T cells. Furthermore, these results highlight the importance that environmental factors may have on the ability of DC subsets to influence Th responses qualitatively; i.e., the ability to drive Th1 versus Th2 differentiation may not be fixed immutably for each DC subset.
树突状细胞（DCs）对于启动免疫反应至关重要。DCs的这种抗原呈递功能在一个称为成熟的过程中按顺序发展，在此过程中它们成为幼稚T细胞的有效致敏剂，但会降低其捕获和处理抗原的能力。小鼠DC群体存在一些异质性，基于CD8α表达可识别出两个表达高水平CD11c的不同DC亚群。我们研究了小鼠脾脏CD8α(-)和CD8α(+) DCs的表型和成熟状态。发现这两个亚群在脾脏中均以未成熟细胞形式存在，并在含GM-CSF的培养基中体外培养或在体内对脂多糖产生反应时经历表型成熟。体外和体内分析表明，这种成熟过程是DCs获得其T细胞启动能力的绝对必要条件，可将CD8α(-)和CD8α(+) DCs转化为幼稚CD4(+)和CD8(+) T细胞的有效且同等高效的激活剂。此外，这些结果突出了环境因素对DC亚群定性影响Th反应能力可能具有的重要性；即驱动Th1与Th2分化的能力可能并非每个DC亚群都固定不变。
