Localization of H-2 antigens on mouse trophoblast cells.

The presence of H-2 antigens of the paternal and maternal haplotypes on mouse trophoblast cells was examined at several stages of pregnancy by using a sensitive immunolabeling technique followed by quantitative radioautography. Results revealed the presence of H-2 antigens (determined by the K or D loci) of both parental haplotypes on the F1 trophoblast cells. At 14-16 d of gestation, the antigen density was equivalent to that on adult thymocytes and there was a further 50% increase on day 18. H-2 antigens of both parental haplotypes are also found to be expressed on 11-13 d trophoblast cells.

Localization of paternal H-2K antigens on murine trophoblast cells in vivo.

We have previously shown the presence of H-2K and D antigens of both parental haplotypes on dispersed murine trophoblast cells. The question still remained whether such antigens are sequestered away from the sinusoidal face of these cells making them inert as allografts. The in vivo expression of H-2 antigens on these cells was therefore examined radioautographically after perfusion of 125I-labeled monoclonal and anti-H-2Kk (anti-paternal) antibody directly into individual placental branches of the uterine artery suppling 15-d-old (C57BL/6J female) X CBA/J male) placentae. Syngeneic C57BL/6J placentae served as negative controls. A radioautographic examination of 0.5-micrometer-thick sections revealed specific labeling of labyrinthine trophoblasts lining the sinusoids of allogeneic placentae. Most of this labeling was localized to the sinusoidal face of the cells as opposed to a weak labeling of the intracellular aspect. Spongiotrophoblasts and trophoblast giant cells did not label, but specific labeling of fetal capillary endothelium and some macrophages was also noted.

MHC antigens on mouse trophoblast cells: paucity of Ia antigens despite the presence of H-2K and D.

The presence of Ia antigens was examined on the surface of trophoblast cells isolated from mouse placentae resulting from mating C57BL/6 female and CBA male mice. A sensitive immunolabeling method was employed in which cells were treated with polyspecific anti-Ia (A.TH anti-A.TL) or monoclonal anti-Ia.17 antibody followed by 125I-labeled protein A and examined with the aid of quantitative radioautography. No appreciable levels of Ia antigens were detectable between days 12 and 17 of pregnancy, although significant amounts of H-2D were always found on the trophoblast cells from the same placentae, and spleen cells as well as thymocytes from control animals always showed the expected degree of labeling for Ia antigens.

Allo-antigenicity of trophoblast cells.

Trophoblast cells of the placenta represent the frontier of the conceptus at the feto-maternal interface, exposed to the maternal immune system. The presence or the absence of major histocompatibility (MHC) antigens on trophoblast cells, thus, is a key determinant of immune interactions between the mother and the allogeneic fetus during pregnancy. This article critically reviews the studies of the alloantigenic status of murine and human trophoblast cells, including the published data in the mouse and unpublished data in the human in the authors' own laboratory. It is shown that, in both these species, a significant proportion of trophoblast cells express Class 1 but not Class 2 MHC antigens in a manner directly accessible to the maternal immune system. However, the lack of immunogenicity of semiallogeneic trophoblast cells can not solely be explained on the basis of the absence of Class 2 molecules, despite the presence of Class 1 molecules. It is proposed either that the Class 1 MHC antigens on the trophoblast cells are presented in a nonimmunogenic manner to the maternal T cells or else that certain cells at the feto-maternal interface (eg, fetally derived trophoblast cells, maternally derived lymphoid cells, or decidual cells) elaborate potent immunosuppressor molecules capable of abrogating T cell alloreactivity.

An evaluation of the maternal natural killer cell population during the course of murine pregnancy.

Earlier work from this laboratory revealed an increase in the level of null (Thy-1-, IgM-) lymphocytes in the maternal lymphoid organs during the first pregnancy in the mouse that was more pronounced during allogeneic pregnancy than during syngeneic pregnancy. In view of the suggestive evidence for the bone marrow origin of these null cells, the functional significance of the null cell rise was explored in this study by an examination of (1) splenic NK activity as measured by the 51Cr-release assay using YAC-1 lymphoma targets, (2) the incidence of NK lineage cells in the spleen as measured by the ability of splenic null lymphocytes to bind YAC-1 lymphoma targets, and (3) the possible presence of a NK target structure on placental trophoblast cells, studied with a cold target competition assay. Results revealed that the absolute levels of null lymphocytes, NK lineage cells, and NK activity in the spleen increased moderately and nearly at the same time during syngeneic pregnancy. During allogeneic pregnancy all three parameters increased more significantly, the rise in the levels of NK activity and NK lineage cells somewhat preceding the null cell rise, suggesting preferential recruitment of active NK cells within the null lymphocyte population of the spleen. Trophoblast cells appeared to share NK target structures with YAC-1 lymphoma cells, suggesting that a rise in the NK cell level in both pregnancy types may represent a response of the mother to such target structures. Since the density of such moieties was similar for homozygous and heterozygous trophoblasts, a higher NK cell response during allogeneic pregnancy is considered to result indirectly from an alloreactive response of the mother to the paternally encoded antigens on the fetoplacental unit, possibly from a stimulation of interferon producing cells such as macrophages. Nevertheless, such a response appears to be harmless for the allogeneic conceptus.

CTL recognize different determinants from those defined serologically on Ld somatic cell mutants.

Reciprocal Ld structural mutants have been isolated from a somatic cell line. Testing of allogeneic CTL clones on these mutants suggests that the majority of CTL clones recognize determinants different from those that elicit antibody production. Of 36 CTL clones tested, only three clones appeared to recognize a determinant that was related to the negatively selected serologic determinant. However, mAb blocking studies suggest that inhibition of CTL activity by anti-H-2 mAb does not necessarily reflect the fine specificity of the CTL activity.