Dendritic cells initiate a two-stage mechanism for T lymphocyte proliferation.
Dendritic cells initiate a two-stage mechanism for T lymphocyte proliferation.
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DOI：
10.1084/jem.157.4.1101
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发表时间：
1983-04-01
期刊：
影响因子：
--
通讯作者：
Palladino MA
中科院分区：
文献类型：
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作者：
Austyn JM;Steinman RM;Weinstein DE;Granelli-Piperno A;Palladino MA
经高碘酸钠氧化后的T细胞以多克隆方式增殖，以响应辅助细胞。我们证实了以前的工作，表明DC是这种反应的有力刺激因素。此外，用特定的单抗和补体清除DC后，小鼠未分离的脾和脾贴壁细胞的辅助功能明显降低。因此，我们以氧化有丝分裂为模型来研究DC刺激T细胞增殖反应的机制。确定了一种两阶段机制。第一个阶段发生在培养的前20h，需要活的DC，包括逐步释放白介素2(IL-2)到培养液中，并获得对该生长因子的反应性。第二阶段发生在20-40h之间，不需要活的DC，并参与了对IL-2的DNA合成。在DC与未修饰的T细胞(同基因MLR)培养过程中也发生了类似的事件，但数量上有所减少。实验方法是将DC和T细胞共培养20h，然后用特异性抗体或抗Ia抗体和补体杀伤DC。如果T细胞在新鲜的培养液中培养，则随后的增殖被抑制。然而，当淋巴细胞在原始DC-T细胞培养液中培养时，或者与粗制或纯化的IL-2制剂一起培养时，淋巴细胞的增殖能力得到恢复。IL-2不能诱导无DC培养的T细胞增殖，也不能与活DC协同作用。我们得出结论，DC通过紧密协调T细胞生长因子或IL-2的释放和应答而诱导增殖。
T cells oxidized with sodium periodate proliferate polyclonally in response to accessory cells. We confirmed previous work showing that DC are potent stimulators of this response. In addition, the accessory function of unfractionated mouse spleen and spleen adherent cells was markedly reduced after elimination of DC with a specific monoclonal antibody and complement. Therefore oxidative mitogenesis was used as a model to study the mechanism by which DC stimulate T cell proliferative responses. A two-stage mechanism was identified. The first stage occurred during the first 20 h of culture, required live DC, and involved the progressive release of interleukin 2 (IL-2) into the medium and acquisition of responsiveness to this growth factor. The second stage occurred between 20 and 40 h, did not require live DC, and involved DNA synthesis in response to IL-2. Similar events occurred during culture of DC with unmodified T cells (syngeneic MLR) but were quantitatively reduced. The experimental approach was to co-culture DC and T cells for up to 20 h and then kill the DC with specific antibody, or anti-Ia antibody, and complement. Subsequent proliferation was inhibited if the T cells were cultured in fresh medium. However, proliferation was restored when the lymphocytes were cultured in the original DC-T cell medium, or with a crude or a purified preparation of IL-2. IL-2 did not induce the proliferation of T cells that had been cultured in the absence of DC, and did not synergize with viable DC. We conclude that DC induce proliferation by tightly coordinating the release of, and responsiveness to, T cell growth factor or IL-2.