EXPRESSION OF NERVE GROWTH-FACTOR AND NERVE GROWTH-FACTOR RECEPTOR TYROSINE KINASE TRK IN ACTIVATED CD4-POSITIVE T-CELL CLONES
EXPRESSION OF NERVE GROWTH-FACTOR AND NERVE GROWTH-FACTOR RECEPTOR TYROSINE KINASE TRK IN ACTIVATED CD4-POSITIVE T-CELL CLONES
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DOI：
10.1073/pnas.90.23.10984
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发表时间：
1993-12-01
影响因子：
11.1
通讯作者：
OTTEN, U
中科院分区：
文献类型：
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作者：
EHRHARD, PB;ERB, P;OTTEN, U
最近的证据表明，神经生长因子（NGF），除了其神经营养功能，作为一种免疫调节剂介导的“串扰”之间的神经元和免疫细胞，包括T淋巴细胞。我们分析了小鼠CD 4 + T细胞克隆表达编码NGF、低亲和力NGF受体和trk原癌基因（NGF的信号转导受体亚基）的转录本的能力。我们发现，两个CD 4+辅助性T细胞（Th）克隆，Th 0型克隆8/37和Th 2型克隆D10.G4.1，表达NGF和Trk mRNA后，适当的激活与促分裂原或抗原和抗原呈递细胞。在活化的8/37 T细胞中，NGF和trk诱导以相似的程度和相似的时间过程发生，提高了NGF和trk基因处于协调控制下的可能性。NGF和NGF受体表达似乎不是所有活化的CD 4 + T细胞的普遍特性，因为Th 1型克隆9/9在任一刺激后不表达任何转录物。在静息和活化的T细胞中缺乏低亲和力NGF受体mRNA意味着低亲和力NGF受体不参与CD 4 + T细胞中的NGF信号转导。我们发现活化的CD 4 + T细胞克隆不仅表达Trk，而且还合成和释放具有生物活性的NGF，这暗示NGF在免疫应答的发展和调节中作为自分泌和/或旁分泌因子。
Recent evidence suggests that nerve growth factor (NGF), in addition to its neurotrophic functions, acts as an immunomodulator mediating ''cross-talk'' between neuronal and immune cells, including T lymphocytes. We have analyzed murine CD4+ T-cell clones for their ability to express transcripts encoding NGF, low-affinity NGF receptor, and trk protooncogene, the signal-transducing receptor subunit for NGF. We show that two CD4+ T-helper (Th) clones, Th0-type clone 8/37 and Th2-type clone D10.G4.1, express NGF and Trk mRNA after appropriate activation with mitogen or with antigen and antigen-presenting cells. NGF and trk induction occurred to a similar extent and over a similar time course in activated 8/37 T cells, raising the possibility that NGF and trk genes are under coordinate control. NGF and NGF receptor expression does not seem to be a universal property of all activated CD4+ T cells, since Th1-type clone 9/9 did not express any of the transcripts after either stimulation. The absence of low-affinity NGF receptor mRNA in resting and activated T cells implies that the low-affinity NGF receptor is not involved in NGF signal transduction in CD4+ T cells. Our finding that activated CD4+ T-cell clones not only express Trk but also synthesize and release biologically active NGF implicates NGF as an autocrine and/or paracrine factor in the development and regulation of immune responses.