NERVE GROWTH-FACTOR PRODUCTION BY LYMPHOCYTES

Nerve growth factor (NGF) is a neurotrophic protein essential for the maintenance and growth of peripheral sympathetic neurons and basal for ebrain cholinergic neurons. Recently, NGF has also been shown to have effects on cells of the immune system. In a search for extra neural so urces of NGF, we detected NGF-specific mRNA in mouse T lymphocytes of both the CD4(+) and CD8(+) phenotypes with the use of an RNase protect ion assay, PCR, and DNA sequence analysis. In CD4(+) cells, NGF was pr esent in both Th1 and Th2 Ag-specific clones, but an increase of NGF-s pecific message was detected after antigenic stimulation only in Th2 c lones. NGF mRNA was also detected in splenic B lymphocytes and in a ce ll line derived from a murine follicular center cell lymphoma. Transla tion into protein and secretion of NGF were demonstrated by Western bl ot analysis. The secreted NGF is in an active form capable of inducing differentiation of PC12 cells into sympathetic-like neurons. Furtherm ore, conditioned medium from clones or lines positive for NGF mRNA was capable of inducing p140 tyrosine kinase autophosphorylation in 3T3 f ibroblasts transfected with cDNA encoding for the tyrosine kinase fami ly NGF receptor. We conclude that lymphocytes synthesize and secrete N GF either as a para-autocrine factor acting on the immune system itsel f, or as a factor for the maintenance of peripheral neurons.