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M Fouchard

Publications and source records attributed to M Fouchard.

27 records · Page 2Linked to original sources

Interferon effect on cytolytic T lymphocytes in a single cycle assay.

In this study we analyse cell-mediated cytotoxicity by the use of 51chromium release and the killer cell enumeration assay. The latter enabled us to estimate cell-mediated cytotoxicity in a single cycle, which confirms the protective effect of interferon (IFN) after target cell treatment. This anti-cytolytic resistance is detected best by microassociation when effector and target cells are separately treated with IFN and associated thereafter. We suggest that, in inflammatory areas, enhanced cytotoxic activity of the IFN-treated effector cells is only operative before the establishment of protection in the targets, which is somewhat slower and appears in about 18 hr. Resistance of the targets could be at least partly attributed to the incapacity of effector cells to bind to them.

Animals

[Polyenzymatic activation of cellular hydrolases induced by interferon; its role in cytolysis and other cellular manifestations induced by interferon].

Interferon (IFN) treatment of human effector T cells activates CMC directed against K562 targets. An increase of the activity of the different hydrolytic enzymes tested (hexosaminidase and acid-phosphatase) measured in the effector cell population parallels cytolysis activation. IFN and IFN inducers (PIC) treatment of cultured murine L-929 cells generate molecular mediated cytolysis. An increase of hydrolytic enzyme activity (hexosaminidase; B-glucuronidase, acid and alkalin phosphatases) precedes cell lysis. Thus, in both cytolytic systems, IFN induced a polyenzymatic activation of hydrolases. This activation is similar to coordinate enzyme induction discovered by Hosli [16] in pathological and experimental instances, when absorbed substrates cannot be hydrolyzed by lack of specific enzymes. Activation of hydrolytic enzymes induced by IFN which determines its enhancing effect on CMC and on fibroblast autolysis [17] could speculatively explain other effects of IFN such as antiviral action, diminution of cell protein synthesis, inhibition of cell division or molecular alterations of cell surface.

Alkaline Phosphatase

Production of human T-lymphocyte clones. I. monoclonal culture and functional cytotoxic maturation.

Well-defined clones of human T-lymphocytes were produced and monoclonal T-cell cultures were maintained for long periods of time. Single T-lymphocytes were isolated with the help of a micropipette from PBL cultures prior to any cellular stimulation (MLC), collected separately at the bottom of a 200 microliter tissue culture microwell under the control of stereomicroscopic observation, and cultured with irradiated lymphoid cells in the presence of TCGF. After 12 days, 20-50% of the seeded wells exhibited clones of 3 x 104-105 T-lymphocytes, which were transferred to larger tissue culture wells (2 ml, LINBRO) for long-term culture. Recloning of the growing cloned cells under the same conditions as the primary culture was carried out successfully. In the preliminary cytotoxic assays performed in 11 clones (a) a marked activity directed against lectin-coated targets was observed in may clones; (b) an important NK-like activity was exhibited by the clone 45B9 (65% of the tested cells lysed K562 cell targets); (c) 2 clones did not demonstrate cytotoxic activity against either PHA-coated L-1210 cells or K562 cell targets. These results could be explained hypothetically by the difference of functional maturation of T-cells within each clone.

Cell Differentiation

Polyenzymatic activation of cellular hydrolases induced by interferon; its role in cell lysis and other interferon--related phenomena.

Treatment of human cultured T cells by interferon (IFN), which enhances cell-mediated cytotoxicity directed against human K562 cell targets (NK-like activity) induces an activation of cell hydrolases. Treatment of mouse cultured L929 cells by IFN and double strand RNA enhancing cell autolysis induces first an activation of tested hydrolases (hexosaminidase, beta-glucuronidase, acid and alkaline phosphatases). Polyenzymatic activation of hydrolases induced by IFN is similar to coordinate enzymatic induction described by Hosli which occurs by lack of specific enzyme when non-digestible substrates are absorbed by cells. It is hypothesized that the polyenzymatic activation which accounts for cell lysis is a general defense mechanism which might also explain other actions related to IFN such as antiviral effect, inhibition of cell division, diminution of protein synthesis and cell surface alteration.

Animals

[Long-term production and culture of clones of human T-lymphocytes].

Culture of blood T lymphocytes collected from normal individuals and cancer patients were carried out in presence of T cell growth factor (TCGF); these cultures presented cytotoxic activity directed against different targets (lectin activated cells, autologous cancer cells, antibody coated cells and K 562). In order to study separately the different effector subpopulations, isolation of single cultured cells were performed with the help of a micropipette under microscope and monoclonal cultures were carried out in presence of TCGF. In the preliminary cytotoxic assays performed in the clones: (1) a marked activity directed against lectin targets was observed in many clones and (2) an important N K activity was exhibited by the clone 45 B9 (65% of the tested cells lysed human lymphoma K 562 cells).

Clone Cells

Evidence for cytotoxic functions in well-defined human T cell clones.

Long-term cultures of T lymphocytes from PBL of normal individuals and cancer patients grown in presence of TCGF exhibited cytotoxic activity directed against a variety of targets. In order to separate the subpopulations responsible for the different cytotoxic activities, cultured T lymphocyte cloning was performed. Production of T cell clones were obtained at a high yield by direct isolation and culture of single T cells. Preliminary analysis of cell-mediated cytotoxicity showed that 8 out of 11 clones were cytotoxic against both PHA pretreated L1210 and K562 target cells. In addition, within a clone, only a percentage of cells expressed the cytotoxic function. We suggested that this finding is due to the different stage of maturation of the cloned cells and this hypothesis correlate with their morphology, which is not identical for all the cells within a clone.

Animals

[Cytolysis through cells dependent on immunization against cellular antigens: identification and enumeration of cytotoxic cells].

In this report we show how to identify and enumerate alloantigen-dependent killer cells. Individual effector cells are associated by micromanipulation to target cells and the doublets are incubated at 37 degrees C. Killers are identified by the lysis of the associated target. Killer cells can be subdivided into two subpopulations: cell responsible for the lysis of the specific target cells which bear the immunizing H-2 antigens and cells which kill only lectin pretreated targets.

Animals

[Clinical usefulness of saralasin in human hypertension (author's transl)].

We have studied the effects of intravenous infusion of saralasin, a competitive antagonist of angiotensin II, in 27 hypertensive patients: 13 had essential hypertension, 14 had renal lesions which involved the renal artery in 9 cases. In essential hypertensives saralasin administration did not significantly lower blood pressure, even after mild salt depletion. It induced a decrease in blood pressure in 7 patients with renal abnormalities (5 with renal artery stenosis, 2 with unilateral parenchymal disease). It may be suggested that in these cases hypertension was dependent, at least partly, on the renin-angiotensin system. In agreement with other investigators, we have found a relationship between the level of plasma renin activity and the blood pressure decrease obtained by saralasin. In patients with unilateral renal artery stenosis, blood pressure decrease was related to renal vein ratio of plasma renin activity.

Adult