Effects of human alpha-foetoprotein on human B and T lymphocyte proliferation in vitro.

Purified human alpha-foetoprotein (AFP) isolated from extracts of foetal and hepatoma tissues, and from cord serum was evaluated as to its suppressive effects on lymphocyte responses to stimuli which selectively trigger human B or T cells. The effects of equivalent concentrations of individual AFP preparations were compared on lymphocyte cultures stimulated with the human B cell mitogen strain Cowan I organisms, with the T cell mitogen phytohaemagglutinin (PHA), and with irradiated allogeneic lymphocytes in the one-way mixed lymphocyte reaction (MLR). PHA responses were significantly inhibited by most purified preparations of AFP in a dose-dependent manner, within the concentration range of 300 to 18 μg/ml. However, individual foetal-derived AFP preparations did vary in suppressive potency on PHA responses, and attempts to reactivate an inactive AFP were unsuccessful. In parallel cultures the mitogenic response to protein A expressing bacteria was normal or even slightly enhanced by AFP. The one-way MLR was effectively suppressed at higher concentrations of AFP (300–600 μg/ml) than were required for inhibition of PHA responses. The inhibitory effect of AFP on PHA-induced lymphocyte proliferation was not altered by increases in the mitogen dose. No evidence was found that AFP merely inhibits PHA responses by direct interference with mitogen or by competition for cell surface receptors with the mitogen. The results reported here indicate that human AFP effectively suppresses certain T cell-mediated reactions, but not B cell responses , and these are in line with previously reported findings in the murine AFP system.