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Biomedical subjects

G Chaouat

Publications and source records attributed to G Chaouat.

At least 145 records · Page 8Linked to original sources
PubMed1982

Regulatory mechanisms in the mixed lymphocyte reaction: evidence for the requirement of two T cells to interact in the generation of effective suppression.

The cellular requirements for suppression of a mixed lymphocyte reaction (MLR) by in vivo alloantigen-activated spleen cells were investigated. We found that the suppression was mitomycin-resistant at days 3 and 5 after antigen injection. By contrast, it was radiation-sensitive on day 3 but not on day 5. Cell fractionation studies using a plate separation technique monitored by flow microfluorometry were performed. We found that neither purified Lyt-2- cells nor purified Lyt-2+ cells independently could suppress an MLR. By contrast, the reconstituted T population was still suppressive. It also was found that culture supernatant factors from allogeneically in vitro restimulated Lyt-2- cells could suppress an MLR if Lyt-2+ cells were present in the responding population. These data obtained by positive selection and reconstitution show that at least two surface immunoglobulin-negative cells interact for the generation of effective MLR suppression. The possibility that we are dealing with a suppressor-inducer, suppressor-effector system is discussed.

Absorption↗
PubMed1982

Modification of thymocytes subsets during pregnancy analysed by flow microfluorometry: role of the alloantigenic status of the conceptus.

Modifications of thymus subsets during pregnancy were monitored using flow microfluorometry and fluorescein-labelled lectins or antibodies. Essentially, it was found that the percentage of peanut lectin-negative (PNA-) cells increased significantly during pregnancy. More interestingly, in the strains tested, the percentage of PNA- cells was more increased in allogeneic than syngeneic pregnancy. This PNA- increase could be mimicked by extracts from syngeneic placenta, but the largest increase in PNA- cells was always observed by injection of allogeneic placental extract, or syngeneic placental extract plus allogeneic cells. These findings suggest that the alloantigenic status of the conceptus does play a role in induction/maintenance of thymus involution, suggesting that it is not a mere hormonal phenomenon and that it could play a role in the events leading to the acceptance of the allogeneic conceptus by the maternal immune system.

Animals↗
PubMed1981

Regulatory T cells in pregnancy. IV. Genetic characteristics and mode of action of early MLR suppressive T cell subpopulations.

The genetic characteristics, surface markers, and mechanisms of action of early-acting, mitomycin-resistant, MLR suppressor T cells from multiparous mouse spleens were studied in MLR of various strain combinations. The cell activity appears to be genetically restricted at the suppressor/reactive cell level, and the major restriction occurs via the IC subregion. However, C3H.OL recombinant pointed toward a possible minor requirement for S-G subregion syngenicity. The suppressor T cell was characterized as an Ia+, Ly1-, Ly2+ subset. The use of Karush double chambers as well as of supernatants of regulated MLR provided evidence that the suppressor cells act via soluble product(s).

Animals↗
PubMed1981

Regulatory T cells in pregnancy. III. Comparison of early acting and late acting suppressor T cells in MLR: evidence for involvement of differential T-cell subsets.

The properties of mitomycin-treated and untreated spleen cells from allopregnant mice (bearing allogeneic foetuses) have been compared for suppressive activity of mixed lymphocyte reaction (MLR) of maternal strain spleen cells responding to paternal (or genetically related) strain cells. Mitomycin-treated cells in 1% normal mouse serum suppress an MLR if added at its onset while they cannot alter an already set up (day 2) MLR. Conversely untreated spleen cells are unable to affect an MLR if added at its onset while they suppress it when added on day 2 of an ongoing MLR. The two systems also differ in their in vitro retriggering requirements at the target cell (stimulator) level. Whereas the untreated, late acting population, in a k/d or k/a system, requires the contact with molecules coded by 'S-G' (or IC+S G) subregion, also present in the father's strain, the mitomycin-treated, early acting population, tested on similar panel does first appear non-specific. Suggestive evidence, however, is given that this apparent non-specificity may in fact veil clones of cells with specific recognition of 'private' Ia determinants. It is suggested that allopregnant mice elaborate two T suppressor cells, acting at different steps of the MLR. The usefulness of the first set (mitomycin-resistant suppression) for exploring the Ia chart is pointed out.

Animals↗
PubMed1980

Regulatory mechanisms of cell-mediated immunity in allogeneic pregnancy.

The transfer of cells from allopregnant animals to syngeneic receivers allografted with paternal strain tumor leads to mild but significant enhancement. The effect can be defined as T cell mediated. Cells from allopregnant animals can suppress a mixed lymphocyte reaction (MLR) of maternal responders against paternal stimulators. The effect relies upon a THY 1+, Ly 2+, Ia+ cell. Cell-mediated lympholysis (CML) assay could also be suppressed by cells from allopregnant animals. Placental products are capable of interfering with allograft rejection in vivo. They can block MLR in vitro, and seem to act in part via the induction of suppressor cells. The respective roles of these depressive components, together with enhancing antibodies, is discussed.

Animals↗
PubMed1980

Regulatory T-cell subpopulations in pregnancy. II. Evidence for suppressive activity of the late phase of MLR.

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.

Animals↗
PubMed1979

[Identification of cytotoxic cells responsible for lysis of target cells pretreated with concanavalin A in spleen populations of pregnant mice with suppressive activity].

During an alloimmunization, killer cells which lyse target cells only in the presence of a lectin are generated. That these cells, as well as suppressive cells, share immunocytological properties with specific killer cells, leads to the hypothesis that these cells may be concerned with the mechanism of immunosuppression. Two experimental results presented in this paper are consistent with this hypothesis: 1) Spleens from H-2k mice pregnant by H-2d males which bear a high suppressive activity also contain a relatively large number of killer cells having the ability to lyse Concanavalin A treated target cells and 2) supernatants of suppressive systems generated through an MLC block the cytolysis of specific target cells by the bound killer cells.

Animals↗
PubMed1979

Regulatory T cell subpopulations in pregnancy. I. Evidence for suppressive activity of the early phase of MLR.

Previous in vivo experiments have provided evidence of suppressive activity induced by multiple allogeneic pregnancies. The reactivity of maternal spleen cells toward paternal strain alloantigens was investigated by use of MLR microculture technique. A study of the kinetics of the MLR showed an early peak of reactivity (48-hr culture) followed by a decline leading to a decreased reactivity by 96 hr when spleen cells from allogeneically pregnant mice were compared to those of virgin or even isogeneically pregnant mice, suggesting the possible action of MLR regulatory cells. A strong suppression of a H-2k (CBA) anti-H-2a (A/J) or anti-H-2d (C57BL/Ks) MLR was observed when mitomycin-treated spleen cells from CBA mice multiparous by A/J or C57BL/Ks (but not CBA) males were added to the culture. This suppression was abolished by treating the regulatory cell population with anti-theta serum plus complement or replacing the 1% normal mouse serum in the medium by a proper antiidiotypic mouse serum.

Animals↗
PubMed1979

Facilitation reaction (enhancing antibodies and suppressor cells) and rejection reaction (sensitized cells) from the mother to the paternal antigens of the conceptus.

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.

Animals↗