THE INFLUENCE OF NERVE GROWTH-FACTOR ON THE INVITRO PROLIFERATIVE RESPONSE OF RAT SPLEEN LYMPHOCYTES

Splenic lymphocytes and accessory cells express receptors for nerve growth factor (NGF), a well-characterized neurotropic peptide that influences the development and survival of neuronal elements in the central and peripheral nervous systems. In the present study, we report that when rat splenic mononuclear cells (MC) are incubated in the presence of NGF, a dose-dependent increase in DNA synthesis occurs during 96-120 hours of culture as measured by 3H thymidine (3H-Thd) uptake. The minimal molar concentration of NGF at which the increased proliferative response of the cells (3.7 nM) is seen corresponded to the equilibrium dissociation binding constant of the MC (Kd = 2.5 nM), suggesting that the response was a conseqeunce of receptor-ligand interaction. In addition, NGF was able to potentiate the lymphoproliferative response to several T-cell and B-cell mitogens. Significantly increased 3H-Thd uptake by NGF-stimulated cells was noted for concanavalin A (Con A), phytohemagglutinin (PHA), and lipopolysaccharide (LPD), particularly at suboptimal dosages of mitogen. Thus it appears that the NGF receptors on rat splenic MC are physiologically relevant and that NGF can modulate proliferation of T- and B-cells.