Hanada K, Tsunoda R, Hamada H
Department of Molecular Biotherapy Research, Cancer Institute, Tokyo, Japan.
J Leukoc Biol. 1996 Aug;60(2):181-90. doi: 10.1002/jlb.60.2.181.
Dendritic cells (DC), with their potent antigen-presenting and accessory activities, are involved in the stimulation of naive T cells. To examine the biological functions of DC, we developed a method for generating large numbers of murine splenic DC. First, DC were propagated in vivo by using a granulocyte-macrophage colony-stimulating factor-secreting tumor as a continuous in vivo source of the cytokine. The DC enriched in the spleen, especially in the white pulps, were purified after an overnight culture. We could reproducibly obtain 6 to 10 X 10(6) splenic DC per mouse. These DC were morphologically similar to interdigitating cells, expressed high levels of MHC class II and costimulatory molecules, and were highly allo-stimulatory in mixed lymphocyte reactions. Further analysis on T cell stimulation activity revealed that the DC had strong costimulatory activity on human T cells. Activated B cells, which express both B7-1 and B7-2, had little T cell costimulatory activity under the same assay conditions. A human histiocytic leukemia cell line, U937, that showed only weak costimulatory activity by itself, worked synergistically with DC and further intensified the T cell stimulation by DC. These findings suggest the presence of a T cell costimulation mechanism in DC, which is activated synergistically by monocytes or macrophages, and deserves further study.
树突状细胞（DC）具有强大的抗原呈递和辅助活性，参与幼稚T细胞的刺激。为了研究DC的生物学功能，我们开发了一种生成大量小鼠脾DC的方法。首先，通过使用分泌粒细胞巨噬细胞集落刺激因子的肿瘤作为细胞因子的持续体内来源，在体内扩增DC。过夜培养后，纯化富集在脾脏中，特别是白髓中的DC。我们可以重复地从每只小鼠获得6至10×10⁶个脾DC。这些DC在形态上类似于交错突细胞，表达高水平的MHC II类分子和共刺激分子，并且在混合淋巴细胞反应中具有高度的同种异体刺激活性。对T细胞刺激活性的进一步分析表明，这些DC对人T细胞具有强大的共刺激活性。在相同的检测条件下，表达B7-1和B7-2的活化B细胞几乎没有T细胞共刺激活性。人组织细胞白血病细胞系U937本身仅表现出微弱的共刺激活性，它与DC协同作用并进一步增强DC对T细胞的刺激。这些发现表明DC中存在一种T细胞共刺激机制，该机制可被单核细胞或巨噬细胞协同激活，值得进一步研究。
