Suppression of primary and secondary autologous mixed lymphocyte reactions by murine alphafetoprotein

The relatively strong proliferative responses that result from the co-culture of responder T and stimulator non-T cell populations separated from the lymphoid tissues of genetically identical mice have been termed autologous mixed lymphocyte reactions (AMLR). These responses are believed to reflect the normal existence of self reactive T lymphocyte clones which are prevented from establishing pathological autoimmune processes in vivo by the presence of effective regulatory mechanisms. Neonatal thymocytes belonging to the Lyt 1+23-T cell subset are shown here to possess an exceptionally efficient capacity to respond against non-T Ia+ spleen cells from adult mice of the same inbred strain. Moreover, AMLR-primed neonatal thymocytes can be restimulated to give a response with the magnitude and kinetics characteristic of a secondary MLR. Murine AFP, which has been previously demonstrated to exert highly selective immunoregulatory effects on allogeneic MLR, is shown here to be capable of essentially abrogating primary and secondary AMLRs in concentrations that can be considered physiological with respect to the endogenous serum AFP levels in the fetus and newborn. Purified AFP isolates of human and rat origin were also demonstrated to have significant inhibitory effects on the murine AMLR. We therefore suggest that endogenous levels of AFP in the fetus and newborn may play an important role in the control of autoreactive lymphocyte functions. Consistent with this idea is the finding that neonatal thymocyte AMLR activity disappears with increasing age in parallel with normal physiological decay in serum AFP levels.