Regulation of human lymphocyte activation by alpha-fetoprotein. Evidence for selective suppression of Ia-associated T-cell proliferation in vitro.

The immunoregulatory effects of purified human fetal- and hepatoma-derived AFP have been evaluated on allogeneic and autologous mixed lymphocyte reactions (AMLR). In striking contrast to the weak or negligible inhibitory effect on allogeneic reactions, the relatively vigorous proliferative activity of normal human T lymphocytes responding to irradiated autologous non-T stimulator cells was found to be highly sensitive to AFP-mediated suppression. Thus, the addition of purified AFP to AMLRs in concentrations that can be considered physiological with respect to the levels normally detected in fetal and newborn sera reduced the proliferative response by as much as 80 to 90 per cent of control responses occurring in the presence of equivalent amounts of albumin. Consistent immunosuppressive effects were observed in tests with six individually isolated preparations of AFP and no significant differences were evident in the inhibitory potency of fetal versus hepatoma AFP. AMLRs were also shown here to be more susceptible than allogeneic reactions to the blocking effect of anti-Ia antibodies. Therefore, on the basis of our present findings we suggest that an important, and perhaps primary function of AFP may be to control Ia-associated autoreactive T cell proliferation during early ontogeny. Consistent with this reasoning is our finding that most of the strong immunosuppressive action of cord serum on AMLR is abrogated by the selective removal of AFP.