Effects of α-Fetoprotein on Murine Immune Responses

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Abstract
Because of the current interest in the possible “immunosuppressive” effects of α-fetoprotein a systematic study of the effect of normal sera, amniotic fluid (AmF), sera from hepatoma-bearing animals (Tu sera), and AFP isolated by immunoabsorption from AmF or Tu sera on various models of the immune response of the mouse was carried out. Whereas some in vitro reactions were inhibited by AFP, other in vitro systems were only weakly inhibited, unaffected, or even enhanced by the addition of AFP. AFP by itself was mitogenic for murine lymphoid cells, inhibited the LPS mitogenic response 3-fold, but did not affect the response to Con A. Very high concentrations of AFP partially inhibited primary in vitro plaque-forming cell (PFC) responses to sheep red blood cells (SRBC). The secondary in vitro PFC response to keyhole limpet hemocyanin (KLH) conjugated to trinitrophenol (TNP) was inhibited 2- to 4-fold. The induction of cytotoxic effector cells directed against P815 mastocytoma cells was increased 9-fold in the presence of AFP. There was no significant difference between the effect of AmFAFP and TuAFP on any of the in vitro reactions studied. Normal and tumor sera produced a similar reduction in secondary PFC responses in spite of a 6000-fold difference in AFP concentration. The in vivo PFC response to SRBC in mice bearing a transplantable hepatoma was greater than that of normal mice even though the serum AFP concentration of the tumor-bearing mice was 1000 times normal. In addition, no AFP synthesis or coating of lymphocytes was observed during the course of a graft-vs-host or mixed lymphocyte reactions. Therefore, although some effects on immune phenomena occur upon addition of serum proteins and AFP, these data do not support a general immunosuppressive role for AFP in the mouse.

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