INHIBITION OF MITOGEN-ACTIVATED PROLIFERATION OF HUMAN-LYMPHOCYTES IN-VITRO BY HIGH-CONCENTRATIONS OF GLUTAMINE

We investigated the influence of high concentrations of glutamine and asparagine on ''in vitro'' cellular growth of lymphocytes stimulated w ith phytohaemagglutinin (PHA), concanavalin A (Con A) and pokeweed mit ogen (PWM), a recognized test of cellular immunocompetence. Human peri pheral lymphocytes were cultured in flat-bottomed 96-well microplates at 37 degrees C for 96 (PHA and Con A) or 144 hours (PWM) in the prese nce of a mitogen at different concentrations and either glutamine or a sparagine supplemented at doses of 2, 4 or 8 mM. Lymphocyte reactivity , measured by the incorporation of tritiated thymidine into cellular D NA, was compared to identical cultures in the absence of supplemented amino acids (controls). We found that glutamine in doses of 2 mM and h igher inhibited lymphocyte proliferation of mitogen-stimulated human l ymphocytes, whereas asparagine caused no effect. These results demonst rate that, although necessary for cellular division in moderate amount s, glutamine in high concentrations has the reverse effect.