Selective immunoregulatory properties of α-fetoprotein

  • Robert A. Murgita
  • Hans Wigzell


It is clear from the findings summarized in this presentation that AFP is endowed with the capacity to exert strong and highlyselective immunoregulatory forces on the immune system. Extensive studies in both the murine and human systems indicate that AFP, in its purified form, can effectively suppress certain. T cell-mediated immune reactionsin vitro while leaving others unaffected or even sometimes enhanced. Existing evidence suggests that AFP does not act to effect B cell functions directly. Possible regulatory influences by AFP on macrophages, natural killer cells and non-lymphoid cell types have not been excluded. In addition to cellular restrictions, studies in the murine system have shown that well-defined immunogenetic laws govern AFP-mediated immunosuppression. Thus, AFP can be expected to be a highly efficient inhibitor of T cell proliferation dependent on the recognition of I region histoincompatibilities, whereas proliferative responses induced by MHC SD region determinants and I region-independent non-MHC differences will remain generally unaffected. A primary site of action by immunosuppressive AFP would seem to be at the level of helper T cells required for antibody synthesis to thymus-dependent antigens and for effective LD-SD collaboration with precursors of cytotoxic T killer cells in the generation of cell-mediated lympholysis. While theimmunosuppressive properties of AFP have now been well substantiated, it is quite possible that theenhancing effects of AFP, which have sometimes been observed on certain types of immune reactionsin vitro, may also be a physiologically relevant phenomenon. A growth-promoting effect by AFP on distinct cell types would be consistent with its frequent association with rapidly dividing cell populationsin vivo, and may to some extent refiect a shared property with albumin, a closely related protein considered essential for growth of mammalian lymphocytesin vitro. Another more specialized manifestation of the lymphocyte-activating property of AFP is the capacity to induce highly efficient inhibitory T cells. Indeed, recent findings support the probable identity between naturally-occurring suppressing T cells in the newborn with high intrinsic levels of AFP and T cells activated by the incorporation of purified AFP into the tissue culture medium of normal adult T lymphocytes, the strong implication being that inhibitory T cells present during the neonatal period are induced by endogenous immunoregulatory AFP molecules. This contention is supported by the fact that such inhibitory T cells can be generated and shown to functionin vivo in normal adult animals injected with purified AFP. Apparent failures to demonstrate immunosuppressive activity by AFP have been reported and variously attributed to: a. differences in methodology used to isolate and test the protein, b. the source of the protein (tumour vs. fetal-derived), c. a unique immunosuppressive molecular subspecies which undergoes post-synthetic modification, and d. loss of active moieties during purification which are normally bound to AFP in the native state. Known cellular and genetic restrictions in the immunoregulatory activity of AFP must, however, also be taken into account in the interpretation of results failing to demonstrate AFP-mediated suppression. Futher detailed investigations are necessary to determine which, if any, of these variable factors can satisfactorily explain presumed inconsistencies in the literature. Nevertheless, on the basis of the large body of information presently available it is possible to conclude, with a high degree of certainty, that AFP does indeed mediate extremely selective and powerful immunoregulatory influences on immune systemsin vitro which are likely to reflect important naturally-occurring regulatory pathwaysin vivo. This has particularly important implications with respect to our understanding of the immunological basis for the maternal/fetal relationship. Furthermore, since AFP may be an agent which can selectively allow the production of a particular immune function, but not another, it may serve as a beneficial tool for immune manipulation with practical as well as theoretical importance.

Key words

B cell functions Embryonic protein Immunoregulation Pregnancy Suppressor cells T cell functions 


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Copyright information

© Springer-Verlag 1979

Authors and Affiliations

  • Robert A. Murgita
    • 1
  • Hans Wigzell
    • 2
  1. 1.Department of Microbiology and ImmunologyMcGill UniversityMontrealCanada
  2. 2.Department of Immunology, Biomedical CenterUniversity of UppsalaUppsalaSweden

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