Regulation on murine T cell responses to autologous antigens by alpha-fetoprotein

Murine α-fetoprotein (AFP), a major component of fetal and newborn sera, was shown to exert potent immunosuppressive effects on autologous mixed lymphocyte reactions (AMLR) in vitro. Thus, the relatively vigorous proliferative response of newborn CBA/J thymocytes reacting in mixed cultures against adult syngeneic spleen cells was almost totally abrogated by 200 and 100 μg/ml AFP over the 6-day time course studied, with significant suppression still evident in the presence of 10 μg/ml AFP. In contrast, the maximum achievable suppression of parellel allogeneic MLRs was only 40 to 60%. The newborn thymocyte anti-adult syngeneic spleen AMLR was shown to be mediated by an Lyt 1⁺23^? T-cell subset reacting against Ia⁺ adult non-T stimulator cells. Newborn and adult AMLRs resulting from autochthonous T responder/non-T stimulator cell mixtures from individual animals were also found to be highly sensitive to AFP-mediated suppression. The fact that fetal-derived AFP could be shown to efficiently inhibit neonatal thymocyte responses to autologous antigens when tested in vitro in amounts 20 to 50 times lower than the levels present in fetal and newborn sera suggests a potentially important role for endogenous AFP in the regulation of autosensitization during ontogeny.