Bertho N, Drénou B, Laupeze B, Berre C L, Amiot L, Grosset J M, Fardel O, Charron D, Mooney N, Fauchet R
Laboratoire Universitaire d'Hématologie et de Biologie des Cellules Sanguines, Institut National de la Santé et de la Recherche Médicale CRI 9606-UPRES EA 22-33, Rennes, France.
J Immunol. 2000 Mar 1;164(5):2379-85. doi: 10.4049/jimmunol.164.5.2379.
Professional APC are characterized by their ability to present peptide via HLA class II in the presence of costimulatory molecules (CD40, CD80, and CD86). The efficiency of Ag presentation can be classed as follows: mature dendritic cells (DC) are most efficient, immature DC and macrophages are intermediate, and monocytes are considered poor APC. There is a large body of evidence demonstrating that HLA-DR transmits signals in the APC. In this study, we have addressed the question of the outcome of HLA-DR signals on APC of the monocyte/DC lineages throughout their differentiation from immature to mature APC. DC were generated from both monocytes and CD34+ cells of the same individual, macrophages were differentiated from monocytes. Immunophenotypical analysis clearly distinguished these populations. HLA-DR-mediated signals led to marked apoptosis in mature DC of either CD34 or monocytic origin. Significantly less apoptosis was observed in immature DC of either origin. Nonetheless, even immature DC were more susceptible to HLA-DR-mediated apoptosis than macrophages, whereas monocytes were resistant to HLA-DR-mediated apoptosis. The mechanism of HLA-DR-mediated apoptosis was independent of caspase activation. Taken together, these data lead to the notion that signals generated via HLA-DR lead to the demise of mature professional APC, thereby providing a means of limiting the immune response.
专业抗原呈递细胞（APC）的特征在于它们能够在共刺激分子（CD40、CD80和CD86）存在的情况下通过HLA-II类分子呈递肽段。抗原呈递效率可分类如下：成熟树突状细胞（DC）效率最高，未成熟DC和巨噬细胞呈中等水平，而单核细胞被认为是较差的APC。有大量证据表明HLA-DR在APC中传递信号。在本研究中，我们探讨了在单核细胞/DC谱系从未成熟APC向成熟APC分化的整个过程中，HLA-DR信号在这些APC上产生的结果这一问题。DC由同一个体的单核细胞和CD34+细胞产生，巨噬细胞由单核细胞分化而来。免疫表型分析能够清晰地区分这些细胞群体。HLA-DR介导的信号导致CD34来源或单核细胞来源的成熟DC显著凋亡。在两种来源的未成熟DC中观察到的凋亡明显较少。尽管如此，即使是未成熟DC也比巨噬细胞更容易受到HLA-DR介导的凋亡影响，而单核细胞对HLA-DR介导的凋亡具有抗性。HLA-DR介导的凋亡机制独立于半胱天冬酶激活。综上所述，这些数据表明通过HLA-DR产生的信号会导致成熟专业APC的死亡，从而提供了一种限制免疫反应的方式。
