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 t o its neurotrophic functions, acts as an immunomodulator mediating ''c ross-talk'' between neuronal and immune cells, including T lymphocytes . We have analyzed murine CD4+ T-cell clones for their ability to expr ess transcripts encoding NGF, low-affinity NGF receptor, and trk proto oncogene, the signal-transducing receptor subunit for NGF. We show tha t two CD4+ T-helper (Th) clones, Th0-type clone 8/37 and Th2-type clon e D10.G4.1, express NGF and Trk mRNA after appropriate activation with mitogen or with antigen and antigen-presenting cells. NGF and trk ind uction 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 no t 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 eithe r stimulation. The absence of low-affinity NGF receptor mRNA in restin g and activated T cells implies that the low-affinity NGF receptor is not involved in NGF signal transduction in CD4+ T cells. Our finding t hat activated CD4+ T-cell clones not only express Trk but also synthes ize and release biologically active NGF implicates NGF as an autocrine and/or paracrine factor in the development and regulation of immune r esponses.