Some previous work has suggested that fetal rejection may be a cause of spontaneous abortion in humans. The aim of the work presented, therefore, was to determine the influence of maternal alloantibody formation against paternal B lymphocytes, detected by the erythrocyte antibody rosette inhibition (EAI) assay, on the outcome of semi-allogeneic pregnancies. Preliminary studies indicated that EA rosette inhibition was a suitable assay for these investigations, because it detected alloantibodies directed to any major histocompatibility complex (MHC) antigen, irrespective of the ability of the antibody to fix complement; this was an important consideration because alloantibodies induced by pregnancy are often only weakly lytic. In humans it was found that antibodies to paternal B lymphocytes occurred significantly more commonly in normal primigravid and multigravid pregnancies when compared with pregnancies of similar gestation which aborted. These antibodies were shown to be directed to MHC encoded antigens by family studies, but were not removed by platelet absorption, strongly suggesting that they were not class I MHC antigens. Studies in inbred rats demonstrated that these paternal antigens were encoded by the RT1A region of the rat MHC alone. Maternal alloantibody responses to RT1A antigens appeared to be suppressive because studies using the rat kidney allograft model showed that multiparous rats with EAI antibodies to paternal strain cells enjoyed prolonged graft survival. It was also found that pregnancies in which the paternal strain differed only by RT1A antigens induced a suppressive immune response in the mother. These results suggest that immune responses to MHC encoded antigens, possibly unique, may prevent fetal rejection in some instances.

<p>Mammalian pregnancy is an immunological paradox. The foetus, which expresses both paternal and maternal cell-surface molecules, has to be protected from rejection by the maternal immune system. At the same time, the mother has to have an efficient immune defence and must provide her offspring with antibodies.</p><p>The first part of this thesis investigates some of the mechanisms involved in the foetal avoidance of maternal rejection reactions. Placental absence of MHC class II expression, as well as a bias for Th2-cytokines at the maternal-foetal interface are suggested to be important for foetal survival. The results showed that placental MHC class II expression cannot be induced <i>in vivo</i>. Transfections of trophoblast cells with MHC class II genes, however, resulted in detectable MHC class II cell-surface expression, indicating that a post-transcriptional block does not exist in these cells.</p><p>By using IL-4- and IL-10-double deficient mice, it was shown that neither maternal nor foetal expression of these cytokines were crucial for completion of allogeneic pregnancy.</p><p>In the second part of the thesis, the effect of transmission of immunoglobulin G (IgG) from the mother to the offspring was studied. It was observed that viable maternal Ig-secreting cells occasionally infiltrated the B cell-deficient offspring and remained functional for long periods. In this study "green fluorescent mice" were used as a tool. Furthermore, neonatal ingestion of wild type milk increased the survival of adoptively transferred B-lineage cells in B cell-deficient mice, suggesting that suckling of IgG-containing milk could be used to facilitate B cell-reconstitution in B cell-deficient mice. Finally, results from studies on normal mice showed that absence of maternal IgG-transmission during their neonatal development resulted in elevated serum-IgG production, as well as enhanced immune reactions upon immunisations in adult life. This showed that maternal IgG can have long-term immunoregulatory effects in the offspring.</p>

Mammalian pregnancy is an immunological paradox. The foetus, which expresses both paternal and maternal cell-surface molecules, has to be protected from rejection by the maternal immune system. At the same time, the mother has to have an efficient immune defence and must provide her offspring with antibodies. The first part of this thesis investigates some of the mechanisms involved in the foetal avoidance of maternal rejection reactions. Placental absence of MHC class II expression, as well as a bias for Th2-cytokines at the maternal-foetal interface are suggested to be important for foetal survival. The results showed that placental MHC class II expression cannot be induced in vivo. Transfections of trophoblast cells with MHC class II genes, however, resulted in detectable MHC class II cell-surface expression, indicating that a post-transcriptional block does not exist in these cells. By using IL-4- and IL-10-double deficient mice, it was shown that neither maternal nor foetal expression of these cytokines were crucial for completion of allogeneic pregnancy. In the second part of the thesis, the effect of transmission of immunoglobulin G (IgG) from the mother to the offspring was studied. It was observed that viable maternal Ig-secreting cells occasionally infiltrated the B cell-deficient offspring and remained functional for long periods. In this study "green fluorescent mice" were used as a tool. Furthermore, neonatal ingestion of wild type milk increased the survival of adoptively transferred B-lineage cells in B cell-deficient mice, suggesting that suckling of IgG-containing milk could be used to facilitate B cell-reconstitution in B cell-deficient mice. Finally, results from studies on normal mice showed that absence of maternal IgG-transmission during their neonatal development resulted in elevated serum-IgG production, as well as enhanced immune reactions upon immunisations in adult life. This showed that maternal IgG can have long-term immunoregulatory effects in the offspring.