EFFECTS OF HUMAN ALPHA-FETOPROTEIN ON HUMAN LYMPHOCYTE-B AND LYMPHOCYTE-T PROLIFERATION INVITRO

Abstract

Purified human .alpha.-fetoprotein (AFP) isolated from extracts of fetal and hepatoma tissues, and from cord serum was evaluated as to its suppressive effects on in vitro lymphocyte responses to stimuli which selectively trigger human B [bone marrow-derived] or T [thymus-derived] cells. The effects of equivalent concentrations of individual AFP preparations were compared on lymphocyte cultures stimulated with the human B cell mitogen, Staphylococcus aureus strain Cowan I organisms, with the T cell mitogen phytohemagglutinin (PHA), and with irradiated allogeneic lymphocytes in the 1-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 300-18 .mu.g/ml. Individual fetal-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 S. aureus bacteria was normal or even slightly enhanced by AFP. The 1-way MLR was effectively suppressed at higher concentrations of AFP (300-600 .mu.g/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. Human AFP apparently effectively suppresses certain T cell-mediated reactions, but not B cell responses in vitro, and these are in line with previously reported findings in the murine AFP system.