Immunosuppressive characteristics of human AFP: effect on tests of cell mediated immunity and induction of human suppressor cells.
Murine AFP has been reported to be immunosuppressive in a variety of systems. However, the extent and degree of inhibition has varied in different species and laboratories. Therefore, we have examined the potential suppressive effect of purified human AFP on several in vitro tests of cellular immunity and the potential mechanism of its action. AFP purified from fetal and liver cancer sera significantly inhibited mitogen and antigen-induced proliferative responses but had no effect on lymphocyte E rosetting, MIF production or mitogen induced T cell cytotoxicity to Chang target cells. Purified human AFP induced human suppressor cell activity, capable of suppressing a one-way mixed lymphocyte reaction (MLC). In contrast to Con A induced suppressor cells, AFP induced suppressor cell activity was overcome by mitogen augmentation of the proliferative response in MLC. These data suggest that the inhibition of lymphocyte proliferation by human AFP may be mediated by the induction of a subpopulation of human suppressor cells. Furthermore, mitogen induced cell mediated cytotoxicity was partially inhibited by primary liver cancer serum and completely inhibited by newborn cord serum, in contrast to purified fetal or tumor AFP which had no effect. These data suggest that there are other immunosuppressive factors in fetal and tumor serum which require further characterization. These other serum factors may be responsible for some of the immunosuppressive effects attributed to AFP. Although AFP is unlikely to play a major immunosuppressive role physiologically in vivo, its selective effect on proliferative responses, apparently mediated by suppressor cells, may prove to be a useful pharmacologic probe of the mechanism of these in vitro lymphocyte responses and biological interactions.
D006801:Humans; D007111:Immunity, Cellular; D007166:Immunosuppressive Agents; D008213:Lymphocyte Activation / Q000187:drug effects; D008214:Lymphocytes / Q000378:metabolism; D008263:Macrophage Migration-Inhibitory Factors / Q000096:biosynthesis; D000509:alpha-Fetoproteins / Q000494:pharmacology*
D007166:Immunosuppressive Agents; D008263:Macrophage Migration-Inhibitory Factors; D000509:alpha-Fetoproteins