The presence of interleukin 4 during in vitro priming determines the lymphokine-producing potential of CD4+ T cells from T cell receptor transgenic mice.
The presence of interleukin 4 during in vitro priming determines the lymphokine-producing potential of CD4+ T cells from T cell receptor transgenic mice.
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DOI：
10.1084/jem.176.4.1091
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发表时间：
1992-10-01
期刊：
影响因子：
--
通讯作者：
Fazekas de St Groth B
中科院分区：
文献类型：
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作者：
Seder RA;Paul WE;Davis MM;Fazekas de St Groth B
为了研究确定CD 4 + T细胞在刺激后是否产生白细胞介素4（IL-4）或干扰素γ（IFN-γ）的因素，我们使用了允许初始T细胞在体外由特异性抗原引发的系统。从表达转基因的小鼠中纯化致密的CD 4 + T细胞，所述转基因编码与I-Ek相关的鸽细胞色素C肽88-104特异性的T细胞受体。这些T细胞在用88-104和抗原呈递细胞（APC）立即攻击时产生非常有限量的IL-4和IFN-γ。然而，在初始“引发”培养（其中在88-104、APC和1，000 U/ml IL-4的存在下孵育4天）之后，T细胞获得了在再激发时产生大量IL-4的能力，但产生非常少的IFN-γ。在不存在IL-4的情况下引发的细胞在再激发时产生IFN-γ，但实际上不产生IL-4。IL-4对IFN-γ产生的抑制作用似乎不是由IL-10产生的诱导介导的，因为向初始培养物中加入IL-10不会抑制IFN-γ产生的引发，抗IL-10也不会阻断IL-4的抑制作用。IFN-γ本身不增加IFN-γ产生的引发，抗IFN-γ也不减少这种引发。然而，当在初始培养物中使用有限量的IL-4（100 U/ml）时，IFN-γ确实减少了IL-4产生的引发。用树突状细胞（DC）、活化的B细胞和I-Ek转染的成纤维细胞作为APC，观察到IL-4在确定致敏细胞的淋巴因子产生表型中的主导作用。然而，不同的APC在其效力上确实不同，DC上级活化的B细胞，活化的B细胞上级转染的成纤维细胞。
To study the factors that determine whether CD4+ T cells produce interleukin 4 (IL-4) or interferon gamma (IFN-gamma) upon stimulation we used a system allowing naive T cells to be primed in vitro by specific antigen. Dense CD4+ T cells were purified from mice that expressed transgenes encoding a T cell receptor specific for pigeon cytochrome C peptide 88-104 in association with I-Ek. These T cells produced very limited amounts of IL-4 and IFN-gamma upon immediate challenge with 88-104 and antigen-presenting cells (APC). However, after an initial "priming" culture in which they were incubated for 4 d in the presence of 88-104, APC, and 1,000 U/ml IL-4, the T cells acquired the capacity to produce substantial amounts of IL-4 upon rechallenge but made very little IFN-gamma. Cells primed in the absence of IL-4 produced IFN-gamma upon rechallenge but virtually no IL-4. The inhibitory effect of IL-4 on IFN-gamma production did not appear to be mediated by the induction of IL-10 production since IL-10 addition to initial cultures did not suppress priming for IFN-gamma production, nor did anti-IL-10 block the inhibitory effect of IL-4. IFN-gamma itself did not increase priming for IFN-gamma production, nor did anti-IFN- gamma reduce such priming. IFN-gamma did, however, diminish priming for IL-4 production when limiting amounts of IL-4 (100 U/ml) were used in the initial culture. The dominant effect of IL-4 in determining the lymphokine-producing phenotype of primed cells was observed with dendritic cells (DC), activated B cells, and I-Ek-transfected fibroblasts as APC. However, the different APC did vary in their potency, with DC being superior to activated B cells, which were superior to transfected fibroblasts.