Inhibition of human lymphocyte transformation by human alpha-foetoprotein (HAFP); comparison of foetal and hepatoma HAFP and kinetic studies in vitro immunosuppression

Abstract

Five pure isolates of human alpha-foetoprotein (HAFP) from adults with tumours of the li er or stomach, as well as HAFP isolated from foetal liver, inhibit in vitro human lymphocyte transformation induced by phytomitogens, anti-human thymocyte serum, and the mixed lymphocyte culture. Foetal HAFP produces 50% inhibition at concentrations of 1-5 mug/ml. The HAFPs isolated from tumour-bearing adults are 1-3 orders of magnitude less potent (50% inhibition achieved at approximately 20, 130, 500, and 2000 mug/ml, respectively). In order to achieve maximum inhibition HAFP must be present at the time of mitogen addition; pre-exposure of lymphocytes to HAFP, followed by washing, does not result in lymphocyte suppression. The inhibiting effect of HAFP cannot be overcome by a ten-fold increase in mitogen concentration implying that HAFP does not act by simple competition with the lymphocyte membrane for the mitogen combining site. HAFP may play an immunoregulatory role during foetal development.