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

We have studied the effects of human alpha-fetoprotein (HAFP), isolated from the serum and ascitic fluid of a hepatoma-bearing patient, 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 anti-human thymocyte serum, but failed to inhibit the response to pokeweed mitogen. HAFP was able to inhibit the one-way mixed lymphocyte culture at concentrations of 250-500 mug/ml, but failed to inhibit at 100 mug/ml. Exposure of lymphocytes to 2.2 mg/ml of HAFP for 18 hr did not result in significant lymphocytotoxicity, and such cells washed free of HAFP were fully capable of participating in the mixed lymphocyte culture. HAFP did not inhibit lymphocyte E-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.