Chaux P, Hammann A, Martin F, Martin M
INSERM, U-252, University of Burgundy, Dijon, France.
Eur J Immunol. 1993 Oct;23(10):2517-25. doi: 10.1002/eji.1830231021.
Although the function and significance of tumor-infiltrating dendritic cells (TIDC) in the immune response to tumor have never been clearly demonstrated, their location suggests that they play a critical role in the presentation of tumor antigen to specific T cells. We studied the morphological and functional characteristics of interstitial dendritic cells (DC) located inside tumors obtained by injection of cancer cells into syngeneic rats. Single and double immunostaining of tumor sections revealed a dense network of cells which expressed class II major histocompatibility complex (MHC II) molecules. Cell morphology and surface markers were characteristic of DC populations in other tissues. These DC were in close contact with tumor cells and increased in number as the tumor grew larger. Unexpectedly, a subpopulation of morphologically characteristic TIDC expressed both CD8 and MHC II molecules. TIDC were purified from tumors by gradient centrifugation and immunobeads and characterized by morphology, ultrastructural study and surface markers studied by flow cytometry. TIDC were negative for the CD5 molecule (a pan T cell marker), and were not labeled with 3.2.3 monoclonal antibody (mAb) (an NK cell marker) or with Ki-M2R mAb (a macrophage marker). A subpopulation of TIDC expressed the CD8 molecule, confirming the in situ results. TIDC expressed high levels of class I and class II MHC molecules and the adhesion molecule ICAM-1. This expression is compatible with effective antigen presenting function. Purified TIDC triggered rapid and high levels of proliferation of tumor-immune T cells in vitro, demonstrating the potential of these cells to constitutively process and present tumor-associated antigens.
尽管肿瘤浸润性树突状细胞(TIDC)在肿瘤免疫反应中的功能和意义尚未得到明确证实,但其位置表明它们在将肿瘤抗原呈递给特异性T细胞的过程中起着关键作用。我们研究了通过将癌细胞注射到同基因大鼠体内所获得肿瘤内部的间质树突状细胞(DC)的形态学和功能特征。肿瘤切片的单重和双重免疫染色显示出一个表达II类主要组织相容性复合体(MHC II)分子的致密细胞网络。细胞形态和表面标志物具有其他组织中DC群体的特征。这些DC与肿瘤细胞紧密接触,并随着肿瘤增大而数量增加。出乎意料的是,一群具有形态学特征的TIDC同时表达CD8和MHC II分子。通过梯度离心和免疫磁珠从肿瘤中纯化出TIDC,并通过形态学、超微结构研究以及流式细胞术研究表面标志物对其进行表征。TIDC对CD5分子(一种泛T细胞标志物)呈阴性,并且未被3.2.3单克隆抗体(mAb)(一种NK细胞标志物)或Ki-M2R mAb(一种巨噬细胞标志物)标记。一群TIDC表达CD8分子,证实了原位结果。TIDC表达高水平的I类和II类MHC分子以及黏附分子ICAM-1。这种表达与有效的抗原呈递功能相符。纯化的TIDC在体外触发肿瘤免疫T细胞快速且高水平的增殖,证明了这些细胞组成性加工和呈递肿瘤相关抗原的潜力。