Effect of Multiparity on Human Maternal Hypersensitivity to Foetal Antigen

Abstract

ALTHOUGH the infant possesses histocompatibility antigens which differ significantly from those of the mother, the foetal allograft manages to survive the period of gestation without being rejected. To explain this apparent paradox of transplantation immunology, Medawar in 1953 advanced several hypotheses¹. These included (1) that the uterus may be an immunologically privileged site; (2) that the foetal antigens are weakly expressed; (3) that there may be an anatomical barrier separating the maternal and foetal circulations, and (4) that pregnancy may be accompanied by some reduction in the immunological capacity of the mother. We have attempted to evaluate one aspect of this problem using an in vitro correlate of cellular hypersensitivity to study the immunological response of the mother's lymphocytes to those of her infant. This technique, the macrophage migration inhibition assay², measures the elaboration of a soluble material, migration inhibitory factor (MIF), from sensitized lymphocytes after stimulation by specific antigen^3,4. Previous work with mice has shown that when peritoneal exudate cells from two genetically different strains were mixed together for 24 h their migration was not inhibited, that is, no MIF was generated, unless one strain had been previously sensitized to the other⁵. In these conditions, the assay appeared to be measuring a cellular immune response indicating prior sensitization. This is in contrast to the response observed in the standard mixed lymphocyte reaction which measures at 5 days the incorporation of ³H-thymidine into lymphocyte DNA. The latter response records an event of primary sensitization between lymphocytes of individuals with different histocompatibility antigens.