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I L Sargent

Publications and source records attributed to I L Sargent.

88 records · Page 5Linked to original sources
PubMed1988

Maternal immune responses to the fetus in early pregnancy and recurrent miscarriage.

Direct evidence that maternal immune rejection of the fetus causes some unexplained recurrent spontaneous abortions was sought in 18 women with this condition. Tests of maternal cell-mediated immunity to fetal (paternal) antigens were done before conception, in early pregnancy, and at miscarriage, and were compared with those in 10 controls in their first pregnancies. Maternal cytotoxic alloantibody production and the blocking effect of maternal sera on maternal lymphocyte activation were also evaluated. There was no evidence for maternal cell-mediated reactivity to paternal antigens in normal early pregnancy or in most women who aborted, but circulating cytotoxic cells were found at miscarriage in a third of affected women. There was no correlation between the production of cytotoxic antibodies and serum blocking activity, and the success of the pregnancy. These data provide evidence that cell-mediated immune reactivity may be changed in some women who abort recurrently but show that circulating immunological blocking factors are not relevant to the success of pregnancy. Their induction by maternal immunisation with paternal leucocytes does not explain why this procedure prevents recurrent spontaneous abortions.

Abortion, Habitual↗
PubMed1988

Cell populations in human early pregnancy decidua: characterization and isolation of large granular lymphocytes by flow cytometry.

Cell populations of human pregnancy decidua, obtained by enzymic digestion from first trimester samples, were analysed by flow cytometry after labelling with monoclonal antibodies. The majority of these decidual cells (75%) were of bone marrow origin. The most abundant cell type expressed antigens characteristic of large granular lymphocytes (LGL), although macrophages and small numbers of classical T cells were also present. Three subsets of decidual LGL can be defined by single-and double-antibody labelling. Most decidual LGL are positive for NKH1, a marker of peripheral blood LGL, but negative for CD16, the Fc receptor of NK cells, and for the T-cell markers CD3 and CD5. About half the NKH1-positive cells also express CD2, associated with the E-rosette receptor, and are identical to the CD3-negative/CD2-positive cells reported previously in early pregnancy decidua. The NKH1-positive cells apparently correspond to a minor subset of peripheral blood LGL. The remaining decidual LGL are positive for CD16 and negative or only dimly positive for NKH1, and are similar to the major type of peripheral blood LGL. After purification by flow cytometry, the NKH1-positive cells were demonstrated to be of similar size to, but slightly higher granularity than, lymphocytes, whereas the CD16-positive cells were larger and more granular. The possible role of decidual LGL in modulating placental development is discussed.

Antibodies, Monoclonal↗
PubMed1987

Maternal cell-mediated sensitisation to paternal HLA may occur, but is not a regular event in normal human pregnancy.

Maternal cell-mediated sensitisation to paternally-inherited fetal HLA was studied in 10 primigravid and 9 multigravid women. One woman in each group was found to have circulating cytotoxic effector cells specific for paternal lymphocytes, but both had a normal pregnancy outcome. These results show that sensitisation is not a regular event in pregnancy and that there must therefore be a block in the afferent (recognition) phase of the mother's immune response. Where sensitisation does occur there must also be a block on the efferent (effector) arm of the response to prevent rejection of the fetus. The restricted distribution of major histocompatibility complex antigens on trophoblast and the function of the placenta as a barrier between maternal and fetal immune compartments can explain the occurrence of both types of blockade.

Cytotoxicity, Immunologic↗
PubMed1987

Leucocyte migration inhibition in diphtheria toxoid hypersensitivity.

A donor who was highly reactive to diphtheria toxoid (DT) in delayed hypersensitivity and in lymphocyte transformation showed scant evidence of antigen-induced inhibition in the direct leucocyte migration agarose test. Other donors, weak or negative to DT in skin test and transformation, did show evidence of inhibition. Although the migration test is useful in assessing cellular reactivity to tubercular antigen, these results question its suitability for DT.

Adult↗
PubMed1986

Immunological disorders of human pregnancy.

Three types of disorders of human pregnancy with a possible immune etiology have been discussed. Pre-eclampsia and recurrent abortion may result from a failure of a maternal immunoregulatory response to trophoblast but the evidence is incomplete and circumstantial. There are several fetal problems which may arise because of transfer of maternal allo-, iso-, or autoantibodies to the fetus. Third, maternal graft-versus-fetal-host disease occurs rarely and may present in a delayed and incomplete way as severe combined immunodeficiency.

Abortion, Habitual↗
PubMed1986

Evidence for a novel HLA antigen found on human extravillous trophoblast and a choriocarcinoma cell line.

We describe the characterization of a novel HLA Class I molecule, which we have isolated from chorionic cytotrophoblast cell membranes, and from a trophoblast-derived choriocarcinoma cell line, BeWo; classical HLA Class I antigens are not expressed on these cells. This antigen is an electrophoretically non-polymorphic glycoprotein of approximately 40,000 molecular weight, which is found in association with beta 2 microglobulin, and which is detected by monoclonal antibodies recognizing monomorphic determinants of HLA Class I. Elucidation of the nature and origin of this molecule may provide valuable information regarding the immune barrier that exists between mother and fetus.

Antigens, Neoplasm↗
PubMed1985

Maternal cell-mediated immunity to the fetus in human pregnancy.

Cell-mediated sensitisation of the mother to her fetus is not a regular event in human pregnancy, and the role of suppressor cells and blocking antibodies in preventing this sensitisation is unresolved. There is as yet little evidence to support the hypothesis that maternal immune recognition of the fetus is essential for the success of the pregnancy. Further progress in this area will depend on systematic investigations of the development of specific maternal humoral and cell-mediated responses to the fetus throughout gestation, and whether a deficiency of these responses results in the failure of the pregnancy.

Binding, Competitive↗
PubMed1983

Maternal cell-mediated immunity in pregnancy--lymphocyte responses of mothers and their non-pregnant HLA identical sisters to paternal HLA.

The mixed lymphocyte reactions (MLR) of normal pregnant women and their non-pregnant HLA identical sisters have been compared, using paternal and unrelated lymphocytes as stimulator cells. Primary and secondary responses were differentiated by studying 7 day MLR time courses. All responses were of a primary nature, with neither stimulation nor suppression of the maternal MLR. These data clearly demonstrate the absence of maternal cellular sensitization to fetal (paternal) HLA.

Fathers↗
PubMed1982

Maternal cell-mediated immunity in normal and pre-eclamptic pregnancy.

Maternal cell-mediated immunity (CMI) to fetal (paternal) HLA was studied in both normal and pre-eclamptic pregnancies. Maternal-paternal mixed lymphocyte reactivity (MLR) was assessed using macrophage migration inhibitory factor (MIF), leucocyte migration inhibitory factor (LIF) and blast transformation assays. Primary and secondary responses were differentiated by studying 6 day MLR time courses. Maternal lymphocytes (normal pregnancies) did not show an early, (i.e. secondary), proliferative response, nor did the pattern of LIF release suggest maternal CMI to fetal (paternal) HLA. However, the lymphocyte responses between pre-eclamptic couples, in terms of both proliferation and LIF release, were consistently and significantly different from those of normal couples; a finding which may reflect an abnormal immune response.

Female↗
PubMed1982

Dual action of leucocyte dialysates and of thymosin on the recovery of sheep-cell-rosetting capacity in trypsinized human lymphocytes.

Trypsinization of human blood lymphocytes abolishes their capacity to form rosettes with sheep erythrocytes (E-rosettes) and this is regained in part on incubation of the cells at 37 degrees C for 3 hr. The recovery of rosetting capacity was found to be accelerated in the presence of dialysable extracts of human leucocytes (DLE) or bovine thymosin fraction 5 (THFV). For both DLE and THFV two types of effect were demonstrated. At lower concentrations the stimulation of recovery was dependent on the presence of the agent during incubation and it presumably comes about through an effect on the metabolic process required for regeneration of the E-receptors. At higher concentrations another mechanism is apparent since the agents were now effective when added after incubation. This last phenomenon is wholly dependent on prior incubation of the trypsinized lymphocytes in medium alone and it probably involves attachment of components of DLE and THFV to incompletely recovered cells, thereby providing a more favourable charge environment for E-rosette formation. A similar process of adhesion-promotion may be occurring in certain in-vitro tests with THFV which are carried out on lymphocytes from immunodeficient patients. On the other hand, it is the other mechanism, that of metabolic action, which is likely to be the predominant consideration in relation to treatment of such patients with DLE or THFV.

Cell Extracts↗
PubMed1980

Effects of human transfer factor on the migration of guinea-pig macrophages: is there an antigen-specific activity?

Dialysable transfer factor (TF) prepared from the buffy-coat cells of tuberculin-positive human donors exerted antigen (PPD)-dependent inhibition of migration of guinea-pig peritoneal exudate cells (PEC) provided that migration of the cells was not strongly affected by PPD alone. TF from tuberculin-negative donors did not do this. The effect could be better demonstrated with tuberculin-sensitive than with normal PEC. Differences in the actions of 'tuberculin-positive' and 'negative' TF may also be seen in the absence of antigen. In a similar but more restricted series of experiments with diphtheria toxoid (DT) as antigen, DT-dependent inhibition was observed only with 'DT-positive' TF. The findings concerning antigen-dependent inhibition in both the tuberculin and toxoid systems are compatible with the concept of an antigen-specific TF, but it is argued that they should not be taken as strong evidence of such specificity. In the tuberculin system the results suggest an alternative explanation, namely that 'tuberculin-positive' TF contains a higher level of a non-specific activity. Whether specific or not, the antigen-dependent activity probably involves a stimulatory action on antigen-induced lymphocyte activation leading to enhanced production of macrophages migration inhibition factor, and it could be related to the 'transfer' phenomenon in vivo.

Animals↗
PubMedDate not supplied

Purification of human cytotrophoblast from term amniochorion by flow cytometry.

Term cytotrophoblast do not express polymorphic MHC Class I antigens, unlike other fetal and maternal cells in the amniochorion/decidua. This allows cytotrophoblast to be isolated and purified from this tissue, utilizing 4E, a monoclonal antibody specific for HLA-B, which labels only non-trophoblast. We have developed a method using enzymic dispersion and Percoll gradient centrifugation, followed by flow cytometry, that yields, on average, a total of 5 X 10(6) term extravillous cytotrophoblast, 97 per cent pure. The availability of highly purified extravillous cytotrophoblast, for the first time, permits precise investigation of trophoblast function.

Antibodies, Monoclonal↗
PubMedDate not supplied

Antigenic heterogeneity of human cytotrophoblast and evidence for the transient expression of MHC class I antigens distinct from HLA-G.

Expression of MHC class I antigens on trophoblast populations in first trimester human chorionic villous tissue was assessed by immunohistology. Antibodies used were W6/32 which recognizes a non-polymorphic framework determinant of HLA- A, -B, -C, MHM5 specific for HLA-B, C and 4E and B23.1 which are specific for HLA-B. Syncytiotrophoblast and villous cytotrophoblast were negative with all the anti (HLA class I) antibodies tested. Interstitial trophoblast cells within the maternal decidua were identified with a new antibody, NDOG5, which is specific for extravillous cytotrophoblast. Double labelling showed that they bind W6/32 but not 4E, MHM5 or B23.1; consistent with the expression of the monomorphic HLA-G. In contrast the cytotrophoblast cells of the cell islands and cytotrophoblast shell, which also express the NDOG5 antigen, were positive with W6/32, 4E, MHM5 and B23.1. Cell column cytotrophoblast cells were negative with all four MHC class I antibodies. These results suggest that differentiation of cytotrophoblast from noninvasive to invasive forms is associated with transient expression of class I antigens other than HLA-G on cytotrophoblast shell and cell island cytotrophoblast.

Chorionic Villi↗
PubMedDate not supplied

The pathogenesis of pre-eclampsia.

Syncytiotrophoblast normally sheds redundant placental debris into the maternal circulation, a process, which depends on apoptosis. It is renewed from the underlying mononuclear cytotrophoblast. We propose that the continual clearance of this debris from the maternal circulation causes a systemic inflammatory response that is present in all pregnant women in the third trimester. Pre-eclampsia occurs when the systemic inflammatory response decompensates. This may occur if the burden of the debris is abnormally high, or if the woman's response to the process is excessive. There is evidence that oxidative stress in the placenta could lead to an overload of debris by stimulating apoptosis or necrosis or both. Such stress would be most likely with spiral artery disease either from deficient placentation or acute atherosis, In this model, deficient placentation is not the cause of pre-eclampsia but a powerfully predisposing condition.

Apoptosis↗
PubMedDate not supplied

Relationships between the developmental potential of human in-vitro fertilization embryos and features describing the embryo, oocyte and follicle.

This paper investigates the relationship of features of in-vitro fertilization (IVF) embryos and the associated oocyte and follicle to the outcome of transfer. It differs from previous studies in including a range of features (n = 53) and in using class probability tree analysis. This is a non-parametric multivariate method which expresses relationships as simple rules of features characterizing the 'take home baby' and 'no take home baby' (negative pregnancy test) classes of embryo batches. Data were analysed retrospectively. Fifty-three (embryo, oocyte and follicular) features for each of the three embryos in the transferred batch were collected for 200 IVF patients. Each batch of three embryos was described by a representative value for each feature. The relationship between features and outcome of transfer was analysed. Only four of the 53 features were identified as predictive. However, an appropriate combination of these four (embryo grade, cell number, follicle size and follicular fluid volume) achieved satisfactory predictivities while offering a simplified and more quantitative basis than regularly used criteria. The key component of the composite embryo grading allotted by embryologists turned out to be cell number. The existing predictive use of follicular size was corroborated and an independent additional predictive contribution of follicular fluid volume was found. The study also suggests that the 49 remaining features have little additional predictive value.

Embryo Transfer↗