Expression of nerve growth factor and nerve growth factor receptor tyrosine kinase Trk in activated CD4-positive T-cell clones.
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.
Ehrhard
P B
PB
Department of Physiology, University of Basel, Switzerland.
Erb
P
P
Graumann
U
U
Otten
U
U
D000818:Animals; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000201:enzymology*; D002454:Cell Differentiation; D002999:Clone Cells; D017931:DNA Primers / Q000737:chemistry; D015870:Gene Expression; D008213:Lymphocyte Activation; D008565:Membrane Proteins / Q000235:genetics; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000378:metabolism*; D015513:Oncogene Proteins / Q000378:metabolism*; D016716:PC12 Cells / Q000166:cytology; D012333:RNA, Messenger / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000235:genetics; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism*
D017931:DNA Primers; D008565:Membrane Proteins; D009414:Nerve Growth Factors; D015513:Oncogene Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D017475:Receptors, Nerve Growth Factor; C065400:oncogene protein trk; D020794:Receptor Protein-Tyrosine Kinases