Roska A K, Lipsky P E
J Immunol. 1985 Nov;135(5):2953-61.
The functions of antigen-presenting cells (APC) in the initiation of T cell activation was examined by culturing antigen-bearing guinea pig macrophages (M phi) with T cells obtained from antigen-primed animals. Although such antigen-bearing M phi stimulated primed syngeneic T cell DNA synthesis, as assessed by tritiated thymidine incorporation, paraformaldehyde fixation (0.15% for 1 min at 37 degrees C) abolished this capacity. Analysis with acridine orange staining indicated that fixed antigen-bearing M phi could not trigger primed syngeneic T cells to progress from the G0 to the G1 phase of the cell cycle. The addition of control non-antigen-bearing syngeneic or allogeneic M phi but not interleukin 1 or 2 to cultures of T cells and fixed APC permitted a proliferative response. Although the interaction between fixed antigen-bearing M phi and responding T cells was genetically restricted, there was no similar restriction for the supplemental control M phi. In fact, completely Ia-negative endothelial cells (EC) and fibroblasts (FB) could restore antigen responsiveness to cultures of fixed antigen-bearing M phi and syngeneic responding T cells, although they could not directly present antigen. Moreover, metabolically intact accessory cells, including Ia-negative EC and FB, could take up and process antigen to an immunogenic moiety, which fixed Ia-positive M phi could present to primed T cells. These data indicate that recognition of the antigen-Ia complex on an APC is necessary but not sufficient to trigger proliferation of freshly obtained primed T cells. The results additionally support the conclusion that APC carry out at least two separate functions necessary for the initiation of antigen-induced T cell activation. Not only must the APC display the antigen-Ia complex, but it must also convey another required effect. This influence, which apparently involved the establishment of cell to cell contact, was neither Ia nor antigen dependent and could only be provided by a metabolically intact cell. By contrast, genetically restricted antigen presentation could be accomplished by a fixed Ia-positive cell. Only when both the antigen-Ia complex and the influence of an intact accessory cell were provided by the same or different accessory cell were T cells triggered to enter the cell cycle.
通过将携带抗原的豚鼠巨噬细胞（M phi）与从经抗原致敏动物获得的T细胞共同培养，研究了抗原呈递细胞（APC）在启动T细胞活化中的作用。尽管通过氚标记胸腺嘧啶核苷掺入评估，这种携带抗原的M phi刺激了致敏的同基因T细胞DNA合成，但多聚甲醛固定（在37℃下0.15%，1分钟）消除了这种能力。吖啶橙染色分析表明，固定的携带抗原的M phi不能触发致敏的同基因T细胞从细胞周期的G0期进入G1期。向T细胞和固定的APC培养物中加入对照的不携带抗原的同基因或异基因M phi，但不加入白细胞介素1或2，可引发增殖反应。尽管固定的携带抗原的M phi与反应性T细胞之间的相互作用受遗传限制，但对照的补充性M phi没有类似的限制。事实上，完全Ia阴性的内皮细胞（EC）和成纤维细胞（FB）可以恢复固定的携带抗原的M phi与同基因反应性T细胞培养物的抗原反应性，尽管它们不能直接呈递抗原。此外，代谢完整的辅助细胞包括Ia阴性的EC和FB，可以摄取和处理抗原成为免疫原性部分，固定的Ia阳性M phi可以将其呈递给致敏的T细胞。这些数据表明，识别APC上的抗原-Ia复合物是触发新获得的致敏T细胞增殖所必需的，但并不充分。结果还支持这样的结论，即APC执行抗原诱导的T细胞活化启动所需的至少两种独立功能。APC不仅必须展示抗原-Ia复合物，还必须传达另一种所需的效应。这种影响显然涉及细胞间接触的建立，既不依赖Ia也不依赖抗原，并且只能由代谢完整的细胞提供。相比之下，遗传限制的抗原呈递可以由固定的Ia阳性细胞完成。只有当抗原-Ia复合物和完整辅助细胞的影响由相同或不同的辅助细胞提供时，T细胞才被触发进入细胞周期。
