Demonstration of the inhibitory effect of human alpha-fetoprotein on in vitro transformation of human lymphocytes.

Abstract

The effects of human .alpha.-fetoprotein (HAFP), isolated from the serum and ascitic fluid of a hepatoma-bearing patient, were studied on the in vitro transformation of human peripheral blood lymphocytes by a variety of mitogenic stimuli. At a concentration of 2.5 mg/ml, HAFP inhibited the lymphocyte response to phytohemagglutinin, concanavalin A and rabbit antihuman thymocyte serum, but failed to inhibit the response to pokeweed mitogen. HAFP inhibited the 1 way mixed lymphocyte culture at concentrations of 250-500 .mu.g/ml, but failed to inhibit at 100 .mu.g/ml. Exposure of lymphocytes to 2.2 mg/ml of HAFP for 18 h did not result in signficant lymphocytotoxicity, and such cells washed free of HAFP were fully capable of participating in the mixed lymphocyte culture. HAFP did not inhibit lymphocyte E [sheep erythrocyte] rosette formation. Fetal HAFP was more effective in inhibiting human lymphocyte responses than hepatoma HAFP. These experiments support the suggestion that HAFP plays an important immunoregulatory role during fetal development, possibly through the suppression of thymus-derived lymphocyte responses to antigenic stimuli. They also suggest that there are important differences in the biological properties of hepatoma and fetal HAFP.