Human CD4+ T cell clones produce and release nerve growth factor and express high-affinity nerve growth factor receptors

Abstract

Background: Increasing evidence shows that nerve growth factor (NGF) plays a role in the complex and fascinating linkage between the nervous and the immune systems due to its ability to modulate functions of several inflammatory cells. Objective: To investigate NGF receptor expression and NGF production and release by human CD4+ cells clones, which have primary relevance in modulating inflammatory events through their different subsets of functional phenotypes. Methods: The expression of NGF and a transmembrane tyrosine kinase (TrkA) was evaluated by immunohistochemistry and flow cytometry analysis in five T H 0, six T H 1, and five T H 2 cell clones derived from human circulating mononuclear blood cells. Moreover, the amount of NGF protein was assessed by measuring the NGF levels in culture supernatants of the T cell clones before stimulation and 48 hours after phytohemagglutinin (PHA) activation by use of an immunoenzymatic assay. Results: Our data have shown that in unstimulated conditions, human CD4+ T cell clones express both immunoreactivity for NGF and the TrkA NGF receptor irrespective of their cytokine profile. Moreover, T H 1 and T H 2 clones, but not T H 0 clones, secrete NGF in basal conditions. PHA activation induces NGF secretion in T H 0 clones and a significant increase of NGF levels in T H 2 ( p < 0.05), but not in T H 1 culture supernatants. Conclusions: Results obtained represent the first evidence of TrkA expression and NGF production and release in human CD4+ cell clones and suggest a possible functional role of NGF in modulating the immune and inflammatory network. (J Allergy Clin Immunol 1997;100:408-14.)