Coulon V, Ravaud A, Gaston R, Delaunay M, Pariente J L, Verdier D, Scrivante V, Gualde N
Laboratory of Immunology, Institut Bergonié, Bordeaux, France.
Int J Cancer. 2000 Dec 1;88(5):783-90. doi: 10.1002/1097-0215(20001201)88:5<783::aid-ijc16>3.0.co;2-m.
Presentation of cell-associated antigen to T cells is a critical event in the initiation of an anti-tumor immune response but it appears to often be deficient or limiting. Here we report an experimental system for stimulation of human T lymphocytes using autologous antigen presenting cells (APCs) and autologous tumor cells. Two types of APCs were prepared from human bone marrow: MC and DC. MC were produced by using GM-CSF and SCF. DC were obtained with the same cytokines plus IL-4. DC and MC were generated in parallel from the same patients and their phenotypes and capacities to prime T lymphocytes were analyzed and compared. MC were CD14+, CD1a-, CD33+ and HLA-DR+. Two populations of DC were defined: immature DC were uniformly CD1a-; mature DC expressed CD1a, CD80, CD86, HLA-DR, CD54 and CD58 but lacked surface CD14. Stimulation of autologous T lymphocytes was studied by measuring their proliferation and cytotoxic function. In more than 80% of our experiments the proliferation of autologous T lymphocytes cocultured with APC pulsed or not with tumor cell lysates was higher than that of T cells cultured alone. DC were more effective than MC in stimulating proliferation of lymphocytes. The capacity of a patient's autologous bone marrow-derived APC to stimulate T cells when exposed to autologous tumor cell lysates suggest that such antigen-exposed APC may be useful in specific anti-tumor immunotherapy protocols.
细胞相关抗原呈递给T细胞是启动抗肿瘤免疫反应的关键事件，但它似乎常常不足或受限。在此，我们报告一种使用自体抗原呈递细胞（APC）和自体肿瘤细胞刺激人T淋巴细胞的实验系统。两种类型的APC由人骨髓制备：MC和DC。MC通过使用GM-CSF和SCF产生。DC通过相同的细胞因子加IL-4获得。DC和MC从同一患者并行产生，并分析和比较它们的表型以及启动T淋巴细胞的能力。MC为CD14 +、CD1a -、CD33 +和HLA-DR +。定义了两种DC群体：未成熟DC均为CD1a -；成熟DC表达CD1a、CD80、CD86、HLA-DR、CD54和CD58，但缺乏表面CD14。通过测量自体T淋巴细胞的增殖和细胞毒性功能来研究对其的刺激作用。在我们超过80%的实验中，与用肿瘤细胞裂解物脉冲或未脉冲的APC共培养的自体T淋巴细胞的增殖高于单独培养的T细胞。DC在刺激淋巴细胞增殖方面比MC更有效。当暴露于自体肿瘤细胞裂解物时，患者自体骨髓来源的APC刺激T细胞的能力表明，这种暴露于抗原的APC可能在特定的抗肿瘤免疫治疗方案中有用。
