Immunocytochemical observation of paraquat-induced alveolitis with special reference to class II MHC antigens.

The expression of class II major histocompatibility complex (MHC) antigens on alveolar epithelial cells and macrophages was investigated immunocytochemically in paraquat-induced alveolitis in the rat lung. Until 2 days after paraquat injection, class II MHC antigens were expressed on the type II alveolar epithelium without any inflammatory cellular infiltration. From the 4th to the 7th day after paraquat injection, class II MHC antigen-positive macrophages increased in the alveolar spaces, whereas the expression on the type II alveolar epithelium became obscure. Over 10 days after the injection, interstitial fibrosis progressed and the intra-alveolar inflammatory infiltrates decreased. Epithelial cells lining the thickened fibrous septa no longer expressed class II MHC antigens. These results suggest that chemical stimuli can induce class II MHC antigen expression on the type II alveolar epithelium in the early stage of cellular injury, followed by inflammatory infiltration and interstitial fibrosis.     

Immunocytochemical observation of paraquat-induced alveolitis with special reference to class II MHC antigens

The expression of class II major histocompatibility complex (MHC) antigens on alveolar epithelial cells and macrophages was investigated immunocytochemically in paraquat-induced alveolitis in the rat lung. Until 2 days after paraquat injection, class II MHC antigens were expressed on the type II alveolar epithelium without any inflammatory cellular infiltration. From the 4th to the 7th day after paraquat injection, class II MHC antigen-positive macrophages increased in the alveolar spaces, whereas the expression on the type II alveolar epithelium became obscure. Over 10 days after the injection, interstitial fibrosis progressed and the intra-alveolar inflammatory infiltrates decreased. Epithelial cells lining the thickened fibrous septa no longer expressed class II MHC antigens. These results suggest that chemical stimuli can induce class II MHC antigen expression on the type II alveolar epithelium in the early stage of cellular injury, followed by inflammatory infiltration and interstitial fibrosis.     

Calbindin-D9k expression in the pregnant cow uterus and placenta

Calbindin-D_9k (CaBP_9k) is a vitamin D-dependent, calcium binding protein first identified in the cytoplasm of the intestinal epithelial cell. Using biotin-streptavidin immunohistochemistry, CaBP_9k was localized to the maternal caruncular epithelium, fetal chorionic epithelium, and trophoblastic binucleated cells of the bovine placenta. Within the maternal epithelium the intensity of staining increases from second trimester pregnancies to term pregnancies, indicating a higher intracellular concentration of CaBP_9k in the epithelium at term. Luminal and glandular epithelium of the non-caruncular endometrium also stained positively for CaBP_9k in all stages of pregnancy observed. No CaBP_9k was identified within the stroma or myometrium of the pregnant cow uterus. The increased level of CaBP_9k in the caruncular epithelium during the last trimester is hypothesized to be in response to the rising demand for calcium to aid in the mineralization of the fetal skeleton. CaBP_9k may play a role in enhancing calcium transport across the placenta in cattle.     

In vivo treatment with interferon-gamma during early pregnancy in mice induces strong expression of major histocompatibility complex class I and II molecules in uterus and decidua but not in extra-embryonic tissues.

Allopregnant (NFR/N [Swiss-derived] H-2q females x 57/Bl H-2b males) and syngeneically pregnant (NFR/N x NFR/N) mice were subjected to daily injections (10(5) U/mouse/day, from Day 5.5 of gestation) of recombinant rat or mouse interferon-gamma (IFNg) in order to investigate its ability to induce extra-embryonic major histocompatibility complex (MHC) expression and antipaternal immune reactions if administered during the first part of the gestation period. In addition, a limited number of IFNg-treated embryo-transferred NFR/N mice carrying C57/B1 embryos (representing a complete allogenic pregnancy) were investigated. Mouse and rat IFNg caused the same type of histological and physiological changes, and most of the experiments were performed by using rat IFNg. Several IFNg-treated mice (irrespective of type of mating) showed a drop in weight and a high rate of resorptions at Day 12.5 of gestation. This interference with pregnancy appeared not to be caused by immunological reactions against the feto-placental unit (no leukocyte infiltration and no significant effect on serum levels of antipaternal antibodies in preimmunized allopregnant IFNg-treated mice). Immunohistochemical stainings of cryosectioned tissues at Day 9.5 of pregnancy revealed that IFNg treatment caused a strong induction of MHC class I and class II expression on most cells in the uterus and on several cells in the maternal decidua, while there was a complete absence of detectable MHC class I and class II expression in the extra-embryonic tissues. Characteristic for a Day 12.5 placenta of an IFNg-treated mouse (including embryo-transferred mice) was a strongly MHC class II-induced maternal decidua and a completely MHC class II-negative fetal placenta. The pattern of IFN-induced MHC class I expression was similar to that of class II, with the exception of class I expression on scattered cells within the basal zone. Thus, the present study provides immunohistological evidence that IFNg administered in vivo during the first part of gestation is not capable of inducing MHC expression on murine extra-embryonic cells despite an extremely high expression of MHC molecules on decidual cells in intimate contact with extra-embryonic tissues. It is likely that the resistance to IFNg-mediated induction of MHC expression on extra-embryonic cells is of basic importance for the protection of mammalian semi-allogeneic fetuses.     

Induction of class II MHC antigen expression on the murine placenta by 5-azacytidine correlates with fetal abortion.

During the gestational cycle the placental tissue does not express class II MHC antigens and whether this phenomenon is important to fetal survival has not yet been evoked. It has been reported that class II antigen expression precedes renal and cardiac graft rejection, which may also be the case in fetal abortion. In a recent report we showed that placental cells can be induced to express class II antigens in vitro and that these cells undergo different regulatory mechanisms depending on their anatomical position in the placenta. Thus, spongiotrophoblast-derived cells express these antigens after interferon-gamma treatment, whereas labyrinthine trophoblast-derived cells are induced by 5-azacytidine. In the present study we examined the effect of 5-azacytidine on class II antigen expression in the placenta and fetal abortion in vivo. We report that 5-azacytidine, when given to pregnant females before the ectoplacental cone formation, dramatically increases fetal loss, which correlates with class II antigen expression in the labyrinthine trophoblast zone. No site effects of 5-azacytidine on placental cell proliferation, splenic T and B cell responses, or reproductive capability of treated females were observed. However, after treatment with 5-azacytidine placental cells can stimulate maternal spleen cells to proliferate in a mixed cell reaction, whereas untreated controls cannot. Furthermore, the abortive effect of 5-azacytidine can be rescued in allogeneic pregnancy by anti-paternal class II monoclonal antibody injection into the animals during the 5-azacytidine treatment. These results suggest that the maintenance of the class II antigen-negative expression on the placenta is indeed necessary to avoid maternal immune attack and ensure fetal survival.     

Immunoregulatory factors contributing to fetal allograft survival.

A mammalian fetus expresses a variety of antigens potentially unknown to the immunologically competent mother. Presented here are the results of investigations of maternal immune reactivity to paternally derived antigens of fetoplacental unit, detected at various levels: 1) spleen and distant lymphatic organs, 2) regional lymph nodes draining uterus, and 3) materno-fetal interface. The results suggest that the mother's immune system reacts differently in semiallogeneic pregnancies than in syngeneic ones. The type of the systemic immune response depends on the stage of pregnancy. Increased percentage of CD8+ cells and decreased CD4+/CD8+ cell ratio was found in distant and regional lymphatic organs during pregnancy. The paternal class I MHC antigens expressed on the trophoblast cells are nonpolymorphic molecules which can have a role in immunotrophism of the placenta and in fetal allograft protection.     

Expression of intercellular adhesion molecule 1 (ICAM-1) on the human oviductal epithelium and mediation of lymphoid cell adherence

The epithelium of the human oviduct expresses the major histocompatibility complex (MHC) class II and shows endocytic properties towards luminal antigens. Therefore, the epithelial cells might behave as antigen-presenting cells, inducing a local immune response. The activation of antigen-specific T cells not only requires presentation of the peptide antigen by MHC class II, but also the presence of co-stimulatory molecules in the antigen-presenting cells. Therefore, the expression of the intercellular adhesion molecule 1 (ICAM-1) was examined in the epithelium of the human oviduct. Most oviducts showed epithelial ICAM-1 expression, as assessed by immunocytochemistry, western blot analysis and RT-PCR assay, and the expression was restricted to the luminal border of ciliated and secretory cells. Interferon gamma, interleukin 1 and lipopolysaccharide treatments increased the percentage of ICAM-1-positive cells in primary cultures, indicating that the expression of ICAM-1 in the oviduct might be upregulated in vivo by inflammatory cytokines or bacterial infections. Binding assays between allogenic phytohaemagglutinin-activated lymphocytes and epithelial monolayers expressing ICAM-1 demonstrated that this molecule stimulated lymphocyte adherence. The presence of ICAM-1, in addition to MHC class II, supports the putative role of the oviductal epithelium in antigen presentation. The exclusive apical distribution of ICAM-1 indicates that T-cell activation would occur in a polarized manner. Binding of lymphoid cells to the surface of the oviductal epithelium may help to retain these immune cells that are required for the clearance of pathogens.     

Involution and regeneration of the endometrium following parturition in the ewe

Involution and regeneration of the endometrium after parturition in the ewe, were studied by light- and electron microscopy. The luminal epithelium in intercaruncular regions of the endometrium remained intact at all stages, but degeneration and death of many glandular epithelial cells were observed on the day after parturition. Glandular regeneration had commenced by 8 d post partum, and the glands were substantially regenerated by 15 d. Caruncular epithelial cells on the maternal side of the placentomes, between the bases of the maternal septa, persisted during the period of degeneration of the foetal and maternal tissues of the placentomes. Epithelial cells from this source contributed to the regeneration of the caruncular epithelium following shedding of plaques of degenerate placental tissue from the caruncles, which commenced after 8 d and was completed before 31 d. Thus, ingrowth of epithelium from the edges of the caruncles, as previously proposed, was not the sole source of new caruncular epithelium. The additional source of regenerating epithelium identified here may account for the rapidity with which epithelium appears in the centres of some caruncles, several millimetres in diameter, during endometrial regeneration. However, in some caruncles, regeneration of the epithelium was not completed until after 31 d post partum.     

Luminal antigens access late endosomes of intestinal epithelial cells enriched in MHC I and MHC II molecules: in vivo study in Crohn's ileitis

In contrast to healthy conditions, intestinal epithelial cells (IECs) stimulate proinflammatory CD4+ and CD8+ T cells during Crohn's disease (CD). The underlying regulatory mechanisms remain unknown. Here we investigated the epithelial expression of major histocompatibility complex (MHC) I and MHC II and its interference with endocytic pathways, in vivo. During ileoscopy, ovalbumin (OVA) was sprayed onto ileal mucosa of CD patients (ileitis and remission) and controls. The epithelial traffic of OVA and MHC I/II pathways were studied in biopsies using fluorescence and electron microscopy. We found MHC I and MHC II to accumulate within multivesicular late endosomes (MVLE) of IECs. Faint labeling for these molecules was seen in early endosomes and lysosomes. MVLE were entered by OVA 10 min after exposure. Exosomes carrying MHC I, MHC II, and OVA were detected in intercellular spaces of the epithelium. OVA trafficking and labeling patterns for MHC I and MHC II in IECs showed no differences between CD patients and controls. Independent of inflammatory stimuli, MHC I and MHC II pathways intersect MVLE in IECs, which were efficiently targeted by luminal antigens. Similar to MHC II-enriched compartments in professional antigen presenting cells, these MVLE might be critically involved in MHC I- and MHC II-related antigen processing in IECs and the source of epithelial-released exosomes. The access of luminal antigens to MHC I in MVLE might indicate that the presentation of exogenous antigens by IECs must not be restricted to MHC II but might also occur as "cross-presentation" via MHC I to CD8+ T cells.     

Involvement of major histocompatibility complex class I compatibility between dam and calf in the aetiology of bovine retained placenta

The possibility was examined that in cattle compatibility of major histocompatibility complex (MHC) products between dam and calf might negatively influence the placental maturation and expulsion, and therefore increase the risk of retained placenta in healthy, normally calving cattle. Fifteen combinations of a single dam and two offspring were selected; the placenta of the first offspring was normally expelled (control) and the placenta of the second one was retained (case). The MHC class I and class II antigens of the animals were typed by immunoprecipitation and by one-dimensional isoelectric focusing (1D-IEF). Compatibility or incompatibility of class I or class II antigens was established by comparison of the IEF banding patterns of dam and calves. Analysis revealed that MHC class I compatibility between dam and calf increased the risk of retained placenta. In this study, the effect of class II compatibility was not significant, nor was the effect of the interaction of class I and class II. In a subsequent, additional sample the experimental design was extended: induction of tolerance against non-inherited maternal antigens (NIMA) might be implicated in the occurrence of the disorder within the group of class I incompatible cases. In three out of the five class I incompatible retained placenta cases, the banding pattern of the incompatible haplotype of the calf was identical to that of the haplotype of the granddam that was not inherited by the dam (NIMA). Notably, within the nine class I incompatible controls, there were none in which the offspring shared a paternal class I type with the granddam. This might suggest a tolerance-inducing effect of NIMA in cattle in relation to retained placenta.(ABSTRACT TRUNCATED AT 250 WORDS)     

Passive immunization against the MHC class I molecule Mamu-AG disrupts rhesus placental development and endometrial responses

The unique MHC phenotype of the human and nonhuman primate placenta has suggested a potential role in maternal-fetal immune tolerance, pregnancy success, and maternal as well as fetal well-being. In the rhesus monkey (Macaca mulatta) a nonclassical MHC class I molecule, Mamu-AG, is a putative homologue of HLA-G and is hypothesized to play a role in maternal-fetal immune interactions during pregnancy. Rhesus monkeys were passively immunized during the second week after implantation with a mAb against Mamu-AG. Passive immunization altered the growth and vascularization of the fetal placenta, the placental modification of maternal endometrial vessels, the maternal leukocyte response to implantation, and the differentiation of epithelial and stromal cells in the endometrium. These data are the first to demonstrate in vivo the importance of MHC class I molecules expressed on primate trophoblasts in establishing an important environment for pregnancy success through coordinated interactions between endometrial and fetal tissues.     

Placentation in garter snakes: scanning EM of the placental membranes of Thamnophis ordinoides and T. sirtalis

Surface topography and cross-sections of the placental membranes were examined by scanning electron microscopy in two species of Thamnophis. The chorionic epithelium of the chorioallantoic placenta consists of broad, squamous cells that lack surface specializations. The apposed uterine epithelium contains ciliated cells and larger, nonciliated cells. Neither the epithelium of the chorion nor that of the uterus is eroded; thus, underlying capillaries are not exposed to the luminal surface. In both the omphaloplacenta and the omphalallantoic placenta, epithelium of the omphalopleure consists of brush-border cells bearing prominent microvilli, interspersed with cells bearing minuscule microvilli. These surface epithelial cells are joined at their apices and their lateral surfaces are extensively sculpted by intercellular channels, presenting the appearance of an epithelium specialized for absorption. Deep to the epithelium lie the yolk spheres of the isolated yolk mass, interspersed with endodermal cells. Surface topography of the uterine epithelia of the omphaloplacenta and omphalallantoic placenta is relatively unspecialized. The acellular shell membrane separates maternal and fetal tissues in each of the three placental types. Marked differences in surface features of the chorioallantois and omphalopleure probably reflect different roles of these membranes in gas exchange and transfer of water and nutrients.     

Increase in 15-hydroxyprostaglandin dehydrogenase activity in the ovine placentome at parturition and effect of oestrogen

Type 1 NAD(+)-dependent 15-hydroxyprostaglandin dehydrogenase (PGDH) is the key enzyme for metabolism of active primary prostaglandins to inactive forms in gestational tissues. The present study examined the activity and immunolocalization of PGDH in the ovine placenta, fetal membranes and uterus over the latter half of pregnancy, and its potential regulation by oestradiol. Placenta, fetal membranes and myometrium were collected from sheep with known single insemination dates on days 70, 100 and 135 of gestation and in active labour demonstrated by electromyographic activity. In addition, chronically catheterized fetuses were infused with oestradiol (100 microgram kg(-1) per 24 h) (n = 5) or saline vehicle into the fetus from day 120 to day 125. PGDH activity measured in placental extracts remained constant from day 70 to day 135 of gestation, and then significantly (P < 0.05) increased by 300% in active labour. Immunoreactive PGDH was localized in the placentome at all stages and was present predominantly in the fetal component of the placentome in uninucleate, but not in binucleate, trophoblast cells. Similarly, in the fetal membranes PGDH immuno-reactivity was present in the uninucleate trophoblast but not in the binucleate cells of the chorion. PGDH immunostaining was also present in the endometrial luminal epithelium, in the smooth muscle of the myometrium, and the glandular epithelium of the cervix. Infusion of oestradiol into the fetal circulation from day 120 to day 125 of gestation had no effect on placental PGDH activity. Immunohistochemistry was used to localize oestrogen receptor alpha in intrauterine tissues to investigate further the failure of oestradiol to increase PGDH activity. Immunoreactive oestrogen receptor alpha was not present in the fetal component of the placenta, although it was expressed in adjacent maternal-derived cells. It is concluded that (1) PGDH activity increases in late gestation; (2) PGDH is expressed in uninucleate trophoblast cells in the ovine placenta and fetal membranes, and also in the maternal endometrial epithelium and stroma, myometrium and cervix; (3) oestrogen receptor alpha is not expressed in fetal cells in the placenta or fetal membranes; and (4) the increase in PGDH activity is not regulated by oestradiol administered to the fetus.     

Invasive equine trophoblast expresses conventional class I major histocompatibility complex antigens

Monoclonal antibodies and alloantisera were used in an indirect immunohistochemical assay to determine the expression of class I and class II Major Histocompatibility Complex (MHC) antigens by equine placental cells and the endometrial tissues at the fetal-maternal interface. MHC class I antigens were expressed at high density on the surface of the trophoblast cells of the chorionic girdle at days 32-36, just prior to their invasion of the endometrium. The mature gonadotrophin-secreting cells of the endometrial cups, which are derived from the chorionic girdle cells, had greatly reduced levels of MHC class I antigen expression while no MHC class I antigens were detectable on the non-invasive trophoblast cells of the allantochorion, except in small isolated patches. MHC class I antigens immunoprecipitated from chorionic girdle cells with either monoclonal antibodies or alloantisera had a relative molecular mass of 44,000, which was identical to that of MHC class I antigens precipitated from lymphocytes with the same reagents. MHC class II antigens were not detected on any trophoblast cells, although they were expressed at high levels by the endometrial glandular and lumenal epithelium immediately bordering the endometrial cups. MHC class I antigens were also expressed at high levels by endometrial tissues in the area of the cups. The high level of MHC class I antigen expression by endometrial glands within and bordering the cups was in sharp contrast to the greatly reduced class I antigen expression by the mature endometrial cup cells themselves.(ABSTRACT TRUNCATED AT 250 WORDS)     

Transfer of antibodies directed to paternal major histocompatibility class I antigens from pregnant mice to the developing fetus

The placental transmission of antibodies directed toward paternal MHC Class I antigens to the developing fetus was studied to assess their effect on the expression of MHC antigens during fetal development and on the development of immune function. 125I-monoclonal anti-paternal MHC antibodies injected i.v. into pregnant mice on day 15 of gestation were efficiently transferred to the fetus within 24 hr in a dose-dependent manner. Biochemical studies on the transferred radioactivity showed that intact antibodies accumulated in the fetus for up to 3 days after antibody injection. During the same period, antibodies were eliminated from the maternal system. The transfer and accumulation of anti-MHC antibodies were independent of the MHC haplotype of the fetus. The pathway of antibody transfer and the localization of transmitted antibodies in the fetus were studied by autoradiographic analysis of the entire fetoplacental unit 24 hr after the injection of anti-paternal MHC antibodies. Our results indicate that antibodies are transferred by way of the placenta and yolk sac, and reach the fetus predominantly via the circulation. Within the embryo proper, the highest levels of antibody were found in the order of blood greater than thymus greater than fetal liver. Most other fetal organs, with the exception of brain and cartilage, showed antibody accumulation, but to a lesser extent. This pattern of antibody distribution over different tissues was similar for allogeneic and syngeneic fetuses. These findings demonstrate that various fetal tissues, including developing lymphoid cells can be directly exposed to the maternally transmitted anti-MHC antibodies, with possible functional consequences on the development of the fetal immune system.     

Ultrastructure of the full-term shark yolk sac placenta. III. The maternal attachment site

During mid- and late gestation, the uterus of sandbar sharks possesses specialized sites for exchange of metabolites between the mother and fetus. Attachment sites are highly vascular, rugose elevations of the maternal uterine lining that interdigitate with the fetal placenta. The maternal epithelium remains intact and there is no erosion. The attachment site consists of a simple, low columnar juxtaluminal epithelium underlain by an extensive vascular network. Juxtaluminal epithelial cells possess branched microvilli, saccular invaginations of the apical surface, and coated pits. They contain numerous coated vesicles, lipid-like inclusions, a prominent rough endoplasmic reticulum, and many free ribosomes. Tight junctions join the luminal aspect of adjacent cells. Lateral cell boundaries are highly folded and interdigitated. Capillaries are closely apposed to the basal cell surfaces. The endothelium is pinocytotically active. Comparison with the uterine epithelium of non-placental sharks, mammalian epitheliochorial placentae, and selected transporting epithelia reveals that the structure of the maternal shark placenta is consistent with its putative multiple functions, viz: (1) nutrient transfer; (2) transport of macromolecules, e.g., immunoglobulins; (3) respiration; and (4) osmotic and ionic regulation.     

Beta2-microglobulin required for cell surface expression of blastocyst MHC

Blastocyst MHC is a mouse MHC class Ib gene that is selectively expressed in blastocysts and placenta like human HLA-G, which protect fetal trophoblasts and some tumor cells from NK cell attack, and in TAP-dependent expression on the cell surface. We expressed blastocyst MHC cDNA in beta2-deficient EL-4 S3 or beta2m-transfected EL-4 S3 cells. In parental EL-4 S3 cells, only 47-kDa blastocyst MHC protein was expressed and retained in the cytoplasm. However, additional 51-kDa blastocyst MHC protein was expressed on the surface of beta2m-transfected EL-4 S3 cells. The 51-kDa protein was resistant to Endo-H, whereas the 47-kDa protein was sensitive for Endo-H. The results suggested that beta2m as well as TAP was necessary for the transportation of blastocyst MHC from endoplasmic reticulum to cell surfaces through the Golgi apparatus, similar to other MHC class I molecules.     

Uterine MHC class I molecules and beta 2-microglobulin are regulated by progesterone and conceptus interferons during pig pregnancy

MHC class I molecules and beta(2)-microglobulin (beta(2)m) are membrane glycoproteins that present peptide Ags to TCRs, and bind to inhibitory and activating receptors on NK cells and other leukocytes. They are involved in the discrimination of self from non-self. Modification of these molecules in the placenta benefits pregnancy, but little is known about their genes in the uterus. We examined the classical class I swine leukocyte Ags (SLA) genes SLA-1, SLA-2, and SLA-3, the nonclassical SLA-6, SLA-7, and SLA-8 genes, and the beta(2)m gene in pig uterus during pregnancy. Uterine SLA and beta(2)m increased in luminal epithelium between days 5 and 9, then decreased between days 15 and 20. By day 15 of pregnancy, SLA and beta(2)m increased in stroma and remained detectable through day 40. To determine effects of estrogens, which are secreted by conceptuses to prevent corpus luteum regression, nonpregnant pigs were treated with estradiol benzoate, which did not affect the SLA or beta(2)m genes. In contrast, progesterone, which is secreted by corpora lutea, increased SLA and beta(2)m in luminal epithelium, whereas a progesterone receptor antagonist (ZK137,316) ablated this up-regulation. To determine effects of conceptus secretory proteins (CSP) containing IFN-delta and IFN-gamma, nonpregnant pigs were implanted with mini-osmotic pumps that delivered CSP to uterine horns. CSP increased SLA and beta(2)m in stroma. Cell-type specific regulation of SLA and beta(2)m genes by progesterone and IFNs suggests that placental secretions control expression of immune regulatory molecules on uterine cells to provide an immunologically favorable environment for survival of the fetal-placental semiallograft.     

Cells of the fetomaternal interface: their role in the maintenance of viviparous pregnancy

An immune system capable of discriminating between self and nonself evolved in nature long before the appearance of the viviparous mode of pregnancy, which brings maternal cells into a direct physical contact with genetically disparate cells of fetal origin. In the hemochorial type of placentation, the former include cells of the maternal immune system. This article briefly reviews the possible mechanisms that may protect the semiallogeneic conceptus in nature, with special reference to the role of the cells at the fetomaternal interface. We also present some new data on the antigenicity of pre- and postimplantation trophoblast cells and the immunobiology of decidual cells. Systemic changes in the maternal immune system appear to represent homeostatic responses to the presence of a semiallogeneic conceptus, unrelated to its protection; mechanisms for this protection must reside locally at the fetomaternal interface. We find that the lack of immunogenicity of the outer (trophoblast) cells of the preimplantation blastocyst can be explained by a transient disappearance of the major histocompatibility (MHC) antigens on their cell surface. However, following implantation and the formation of the placenta, class 1 MHC antigens reappear on certain classes of trophoblast cells, i.e., labyrinthine and spongiotrophoblast cells of the murine placenta. Similarly, cytotrophoblast cells of the early human placenta exhibit the presence of class 1 MHC antigens. An absence of class 2 MHC antigens despite the presence of class 1 antigens cannot entirely explain the lack of trophoblast immunogenicity. A local immunosuppression mediated by trophoblast cells themselves as well as maternal cells of hemopoietic origin in the decidua remain as a strong possibility. Typical decidual cells appear to play a central role in the maintenance of pregnancy because of their numerous functions: nutritive, endocrine, and immunoregulatory. Our studies reveal that they are descendants of bone-marrow-derived precursors, have unique surface markers recognizable with monoclonal antibodies nonreactive with other hemopoietic cell lineages, and have the ability to abrogate mixed lymphocyte reactions in vitro in a genetically unrestricted manner. Further studies directed at the cells of the fetomaternal interface should provide a better insight into the mode of survival of the nature's most commonplace allograft.