Production of transforming growth factor beta by human T lymphocytes and its potential role in the regulation of T cell growth.
Production of transforming growth factor beta by human T lymphocytes and its potential role in the regulation of T cell growth.
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DOI：
10.1084/jem.163.5.1037
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发表时间：
1986-05-01
期刊：
影响因子：
--
通讯作者：
Fauci AS
中科院分区：
文献类型：
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作者：
Kehrl JH;Wakefield LM;Roberts AB;Jakowlew S;Alvarez-Mon M;Derynck R;Sporn MB;Fauci AS
本研究探讨了转化生长因子β（TGF-β）在调节人T淋巴细胞增殖中的潜在作用，并提出TGF-β是一种重要的自身调节淋巴因子，限制T淋巴细胞克隆扩增，T淋巴细胞产生TGF-β在T细胞与其他细胞类型的相互作用中很重要。TGF-β显示出抑制IL-2依赖性T细胞增殖。向IL-2刺激的人T淋巴细胞培养物中加入皮克量的TGF-β抑制了60- 80%的DNA合成。TGF-β抑制IL-2诱导的IL-2和转铁蛋白受体的上调。在静息和活化的T细胞上都发现了TGF-β的特异性高亲和力受体。细胞活化显示在每个细胞的基础上导致TGF-β受体的数量增加五到六倍，而受体的亲和力没有变化。最后，观察到活化的T细胞产生TGF-β mRNA，并且TGF-β生物活性存在于由活化的T细胞调节的上清液中，这是T细胞本身是TGF-β来源的有力证据。发现静息T细胞具有低至不可检测的TGF-β mRNA水平，而PHA活化导致TGF-β mRNA水平快速增加（2小时内）。发现T4和T8淋巴细胞在激活后都会产生TGF-β的mRNA。使用软琼脂测定和竞争性结合测定，在T细胞调节的上清液中发现TGF-β生物活性; T细胞活化导致TGF-β产生增加10-50倍。因此，TGF-β可能是人T细胞增殖的重要抗原非特异性调节剂，并且在T细胞与其细胞功能由TGF-β调节的其他细胞类型的相互作用中是重要的。
This study examines the potential role of transforming growth factor beta (TGF-beta) in the regulation of human T lymphocyte proliferation, and proposes that TGF-beta is an important autoregulatory lymphokine that limits T lymphocyte clonal expansion, and that TGF-beta production by T lymphocytes is important in T cell interactions with other cell types. TGF-beta was shown to inhibit IL-2-dependent T cell proliferation. The addition of picograms amounts of TGF-beta to cultures of IL-2-stimulated human T lymphocytes suppressed DNA synthesis by 60-80%. A potential mechanism of this inhibition was found. TGF-beta inhibited IL-2-induced upregulation of the IL-2 and transferrin receptors. Specific high-affinity receptors for TGF-beta were found both on resting and activated T cells. Cellular activation was shown to result in a five- to sixfold increase in the number of TGF- beta receptors on a per cell basis, without a change in the affinity of the receptor. Finally, the observations that activated T cells produce TGF-beta mRNA and that TGF-beta biologic activity is present in supernatants conditioned by activated T cells is strong evidence that T cells themselves are a source of TGF-beta. Resting T cells were found to have low to undetectable levels of TGF-beta mRNA, while PHA activation resulted in a rapid increase in TGF-beta mRNA levels (within 2 h). Both T4 and T8 lymphocytes were found to make mRNA for TGF-beta upon activation. Using both a soft agar assay and a competitive binding assay, TGF-beta biologic activity was found in supernatants conditioned by T cells; T cell activation resulted in a 10-50-fold increase in TGF- beta production. Thus, TGF-beta may be an important antigen-nonspecific regulator of human T cell proliferation, and important in T cell interaction with other cell types whose cellular functions are modulated by TGF-beta.