CD28-mediated costimulation of interleukin 2 (IL-2) production plays a critical role in T cell priming for IL-4 and interferon gamma production.
CD28-mediated costimulation of interleukin 2 (IL-2) production plays a critical role in T cell priming for IL-4 and interferon gamma production.
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DOI：
10.1084/jem.179.1.299
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发表时间：
1994-01-01
期刊：
影响因子：
--
通讯作者：
Paul WE
中科院分区：
文献类型：
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作者：
Seder RA;Germain RN;Linsley PS;Paul WE
幼稚 T 细胞需要白细胞介素 4 (IL-4) 才能发育为产生 IL-4 的 T 细胞，而 IL-4 会阻止此类细胞发育为干扰素伽马 (IFN-gamma) 产生者。使用抗受体抗体作为激动剂对辅助细胞独立启动系统的先前研究已经证明，IL-2对于在这些培养条件下产生IL-4的细胞的发育也是必需的。在这里，我们使用更生理的模型研究了 IL-2 和 CD28 共刺激途径在引发 IL-4 和 IFN-γ 产生中的作用。这涉及辅助细胞将抗原呈递给来自转基因小鼠的初始 CD4+ T 细胞，这些细胞表达对与 I-Ek 相关的细胞色素 c 肽具有特异性的 T 细胞受体 (TCR)。对于脾抗原呈递细胞 (APC)，融合蛋白 CTLA4-免疫球蛋白 (Ig) 对 CD28 共刺激的抑制阻碍了有效的启动。类似地，表达 MHC II 类和 CD28 配体 B7 的转染成纤维细胞可以引发 IL-4 的产生，并且这种引发也被 CTLA4-Ig 阻断。然而，如果提供外源性IL-2和IL-4，缺乏CD28配体的APC也可以启动TCR转基因T细胞成为IL-4生产者，并且在存在CTLA4-Ig的情况下脾脏或转染的成纤维细胞APC所观察到的启动抑制可以通过添加IL-2来逆转。同样，CTLA4-Ig 可以阻断 IFN-γ 产生的启动，并可以被 IL-2 逆转。因此，我们得出结论，IL-2 在启动初始 CD4+ T 细胞成为 IL-4 或 IFN-γ 生产者方面发挥着关键作用。 CD28 途径的参与虽然通常在这种引发中很重要，但在外源 IL-2 存在的情况下是不必要的。
Naive T cells require interleukin 4 (IL-4) to develop into IL-4- producing T cells and IL-4 blocks development of such cells into interferon gamma (IFN-gamma) producers. Prior studies in accessory cell- independent priming systems using antireceptor antibodies as agonists have demonstrated that IL-2 is also necessary for the development of IL- 4-producing cells under these culture conditions. Here we have examined the role of IL-2 and the CD28 costimulation pathway in priming for IL-4 and IFN-gamma production using a more physiologic model. This involved antigen presentation by accessory cells to naive CD4+ T cells from transgenic mice whose cells express a T cell receptor (TCR) specific for a cytochrome c peptide in association with I-Ek. With splenic antigen-presenting cells (APCs), inhibition of CD28 costimulation by the fusion protein CTLA4-immunoglobulin (Ig) blocked effective priming. Similarly, transfected fibroblasts expressing both MHC class II and the CD28 ligand B7 could prime for IL-4 production and such priming also was blocked by CTLA4-Ig. However, APCs deficient in CD28 ligands also could prime TCR transgenic T cells to become IL-4 producers if an exogenous source of IL-2, as well as IL-4, was provided, and the inhibition of priming seen with splenic or transfected fibroblast APCs in the presence of CTLA4-Ig could be reversed by addition of IL-2. Likewise, priming for IFN-gamma production could be blocked by CTLA4-Ig and reversed by IL-2. Thus, we conclude that IL-2 plays a critical role in priming naive CD4+ T cells to become IL-4 or IFN-gamma producers. Engagement of the CD28 pathway, although normally important in such priming, is unnecessary in the presence of exogenous IL-2.