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Humoral and cellular immune agents of a maternal reaction were investigated during pregnancy. Fluorescence studies performed on mouse placentae at 14 days detected maternal immunoglobulins of mainly IgG1 but also IgG2 subclasses. These immunoglobulins, after acid elution, can rebind the placenta and the thymocytes of the relevant paternal strain in case of allogeneic pregnancies, demonstrating an antibody activity towards both placenta specific and paternal strain antigens. They can specifically enhance a paternal strain tumour allograft on a maternal strain recipient. Spleen cells from an allogeneically pregnant mother can reduce or promote paternal strain tumour allograft on a maternal strain recipient. The aggressive effect is shown with small doses of transferred cells, whereas large doses promote enhancement. The suppression of the cytotoxic response of the recipient was ascribed to T cells by use of anti-theta plus complement. Thus, both the rejection reaction (immune cytotoxic cells) and the facilitation reaction (enhancing antibodies and suppressor cells) were demonstrated during pregnancy.

Adding mitomycin-treated spleen cells from an allopregnant mouse to a material-strain cells v. paternal-strain cells MLR was previously shown to decrease the intensity of the reaction, due to suppressor T cells. In the present study, spleen cells from allogeneically pregnant mice, were added without treatment at day 2 of an MLR of maternal strain responder cells raised against paternal-strain stimulators. It was shown that, while, on 2 day duration culture versus the same stimulator cells these cells are hyper-reactive compared to controls, yet they lead to a MLR of lower intensity than when the same operation was performed with control cells. This suppressive effect is T-cell dependent and use of high dilutions of anti-Thy 1+C suggests that the suppressor cell has a high density of Thy 1 surface antigen. Involvement of these cells in negative regulation of the late phase of the MLR is suggested. MLRs with cells from allopregnant mice as responders were themselves susceptible to this suppression and even more so than cells from virgin mice, indicating a possible physiological role.

Present knowledge of the alloantigenic status of the placenta, which makes it a natural semi-allogeneic allograft is briefly surveyed. The systemic immunoregulatory mechanisms operating during normal allopregnancy which are not a prerequisite for a successful pregnancy are recalled. The placenta--dependent local mechanisms, e.g. trophoblast dependent decidual suppressor cells, factor mediated and factor independent resistance to cell mediated lysis, are surveyed as well as some of the mechanisms of action of trophoblast regulatory factors, namely suppressor cell induction and inhibition of IL-2 dependent cell growth/activation. The main feature of the CBA x DBA/2 model of spontaneous abortions in mice, and its prevention by anti Balb/c leukocyte immunisation are described. It was shown that anti-T cell depletion prevents the anti-abortive effects of immunisation. Such a treatment is also able to restore normal placental weight in auto-immune MRL lpr mice, which are known to display excess seric CSF beta-like activity (CSFs being in vitro efficient growth factors for trophoblasts). Transfer of such cells into the MHC compatible CBA/J prevents resorbtions upon a subsequent mating with DBA/2. Thus, direct effects of CSFs beta 1 and beta 2 as anti abortifacient (IL3 and GM CSF) are described together with the abortificacient effects of TNFs and NKs activators.

TNF and LPS can induced labour in mice. In our serial, in induced RU 486 labour, TNF value enhanced 48 hours after RU 486 and decreased after parturition.

The placental immunotrophism hypothesis states that maternal T cells, through their lymphokines, exert a positive influence on placental growth, which can lead to improved chances of fetal survival. We report here that deleting maternal T cells by monoclonal antibody injection during midgestation is accompanied by increased fetal resorption and decreased placental weight and phagocytosis in two different strain combinations of mice. Conversely, mice with T-cell proliferative disease show increased placental weight and phagocytosis, which can be reversed following T-cell depletion during pregnancy. Furthermore, female mice that are prone to fetal resorption show improved fetal survival if injected with spleen cells from mice with T-cell proliferative disease. These results are in accord with predictions of the placental immunotrophism hypothesis and imply that maternal T cells can participate in the prevention of spontaneous fetal resorption.

PROBLEM: The aim of the present study was to define the expression of CXCR4 and CCR5 on non-cultured non-stimulated primary human trophoblast cells (TCs) immediately after their immunopurification. METHOD OF STUDY: We have evaluated by flow cytometric analysis and immunofluorescence, highly purified primary TCs prepared from first trimester (8.2 +/- 0.3 weeks, n = 15) and term (Caesarean section, n = 10) placentae for the cell surface and intracellular expression of CXCR4 and CCR5. RESULTS: There was a high level of individual variability for CXCR4 and CCR5 expression between trophoblast batches. In first trimester and term placentae TCs, we found a greater number of TCs preparations expressing intracellular CXCR4 than CCR5 (P < 0.05). Both receptors were predominantly localized in the intracellular compartment of TCs, whatever if isolated from first trimester or term placentae. CONCLUSIONS: The functional consequences of the predominance of CXCR4 expression and of cellular addressing are briefly discussed.

This paper is a summary of three oral presentations, as well as the ensuing discussion, at the Rijeka/Opatija 3rd Alps Adria Immunology meeting by three members of the European Biomed group on vertical transmission of HIV (G. Chaouat, F. Barre-Sinoussi, G. Scarlatti). This group also involves the laboratories of D. Dormont (CEA, Fontenay aux roses, France), P. Gounon (Electron Microscopy, the Pasteur Institute, France; Irène Athanassakis, University of Crete, Greece; Eva Maria Fenyö, Karolinska Institute, Sweden; and Larry Guilbert, Canada). As such, this paper intends to be neither a review, nor an original article, but rather is an opinion paper discussing the working hypothesis of this network, as well as some of their recent results, which were presented at this meeting. The paper was issued at the request of the organizers of the meeting.

We have investigated the effects of supernatants from human placenta explant cultures on lymphokine dependent T cell proliferation using mainly the CTLL-2 reference murine cell line. A profound, dose dependent, inhibition of both IL-2 and IL-4-dependent cell proliferation was observed. In addition, supernatants from human placental cultures inhibited B cell proliferation, IL-5-driven proliferation of B13 cells, and IL-6-induced proliferation of 7TD.1. Conversely, the supernatants from human placental cultures enhance the growth of human embryonic fibroblasts. Characterization of the material by HPLC yielded a 68-70 kDa peak at pH 7.4, but the peak activity was at a smaller molecular weight (20-25 kDa) if pH 2.9 acetic acid, KC1 buffer was used. The same fractions were inhibitory for IL-2 and IL-4 driven proliferation of CTLL-2 cells. We conclude that the substances tested are acting as a general growth inhibitor for lymphocytes.