Rel-deficient T cells exhibit defects in production of interleukin 3 and granulocyte-macrophage colony-stimulating factor
Rel-deficient T cells exhibit defects in production of interleukin 3 and granulocyte-macrophage colony-stimulating factor
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DOI：
10.1073/pnas.93.8.3405
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发表时间：
1996-04-16
影响因子：
11.1
通讯作者：
Grumont, RJ
中科院分区：
文献类型：
--
作者：
Gerondakis, S;Strasser, A;Grumont, RJ
c - rel原癌基因编码一种类似NF - κB转录因子家族的亚基。缺乏Rel的小鼠在B和T淋巴细胞的有丝分裂原激活方面存在缺陷，并表现出体液免疫受损。为了确定伴随Rel缺失相关的T细胞刺激缺陷的基因表达变化，我们检测了有丝分裂原刺激的Rel（ - / - ）T细胞中细胞表面激活标志物的表达以及细胞因子的产生。在有丝分裂原激活的Rel（ - / - ）T细胞中，包括白细胞介素2受体α（IL - 2Rα）链（CD25）、CD69和L - 选择素（CD62）在内的细胞表面标志物的表达是正常的，但细胞因子的产生受损。在用佛波醇12 - 肉豆蔻酸13 - 乙酸酯和离子霉素刺激的Rel（ - / - ）脾T细胞培养物中，IL - 3、IL - 5、粒细胞 - 巨噬细胞集落刺激因子（GM - CSF）、肿瘤坏死因子α（TNF - α）和γ干扰素（IFN - γ）的水平仅比正常T细胞低2到3倍。相比之下，抗CD3和抗CD28刺激的Rel（ - / - ）T细胞不能增殖，几乎不产生或检测不到细胞因子。外源性IL - 2可恢复抗CD3和抗CD28处理的Rel（ - / - ）T细胞的增殖反应，并将IL - 5、TNF - α和IFN - γ的产生恢复到接近正常水平，但不能将IL - 3和GM - CSF的表达恢复到正常水平。与有丝分裂原激活的Rel（ - / - ）T细胞相反，脂多糖刺激的Rel（ - / - ）巨噬细胞产生高于正常水平的GM - CSF。这些发现表明，Rel可以作为基因表达的激活剂或抑制剂发挥作用，并且是T淋巴细胞产生IL - 3和GM - CSF所必需的。
The c-rel protooncogene encodes a subunit of the NF-kappa B-like family of transcription factors, Mice lacking Rel are defective in mitogenic activation of B and T lymphocytes and display impaired humoral immunity, In an attempt to identify changes in gene expression that accompany the T-cell stimulation defects associated with the loss of Rel, we have examined the expression of cell surface activation markers and cytokine production in mitogen-stimulated Rel(-/-) T cells, The expression of cell surface markers including the interleukin 2 receptor alpha (IL-2R alpha) chain (CD25), CD69 and L-selectin (CD62) is normal in mitogen-activated Rel(-/-) T cells, but cytokine production is impaired, In Rel(-/-) splenic T cell cultures stimulated with phorbol 12-myristate 13-acetate and ionomycin, the levels of IL-3, IL-5, granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor alpha (TNF-alpha), and gamma interferon (IFN-gamma) were only 2- to 3-fold lower compared with normal T cells, In contrast, anti-CD3 and anti-CD28 stimulated Rel(-/-) T cells, which fail to proliferate, make little or no detectable cytokines, Exogenous IL-2, which restitutes the proliferative response of the anti-CD3- and anti-CD28-treated Rel(-/-) T cells, restores production of IL-5, TNF-alpha, and IFN-gamma, but not IL-3 and GM-CSF expression to approximately normal levels, In contrast to mitogen-activated Rel(-/-) T cells, lipopolysaccharide-stimulated Rel(-/-) macrophages produce higher than normal levels of GM-CSF, These findings establish that Rel can function as an activator or repressor of gene expression and is required by T lymphocytes for production of IL-3 and GM-CSF.