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Biomedical subjects

M Kamoun

Publications and source records attributed to M Kamoun.

At least 91 records · Page 5Linked to original sources
PubMed1986

Down regulation of IL 2 mRNA by antibody to the 50-kd protein associated with E receptors on human T lymphocyte.

Recent studies have shown that antibodies to certain epitopes on the 50-kd molecule associated with sheep erythrocyte receptors on human T cells can suppress T cell proliferation and interleukin 2 (IL 2) elaboration. We used a human IL 2 cDNA clone to investigate the effect of antibody 9.6 and cyclosporin A (CsA) on the regulation of IL 2 mRNA levels in the cloned human leukemic T cell line Jurkat, J32. Maximal levels of IL 2 mRNA were reached 6 hr after induction of Jurkat cells with a combination of mitogen phytohemagglutinin (PHA) and phorbol ester (TPA). Antibody 9.6, added during the first 4 hr after lymphocyte stimulation, markedly inhibited IL 2 mRNA accumulation induced by low but synergistic combination of PHA (5 micrograms/ml) and TPA (1.0 ng/ml). The inhibition by 9.6 was not demonstrable as the concentration of PHA or TPA was increased. In contrast, the ability of CsA to suppress IL 2 mRNA accumulation appeared to be independent of PHA or TPA concentration and was minimal if CsA was added 4 hr after stimulation. IL 2 mRNA could be superinduced several folds by addition of cycloheximide 3 hr after induction of J32 with mitogens. Antibody 9.6 did not prevent IL 2 mRNA superinduction induced by cycloheximide, whereas CsA, as well as transcription inhibitor DRB, completely blocked this phenomenon. These findings indicate that signals induced by antibody 9.6 regulate IL 2 production at a pre-translational level, are operative for an extended period of time overlapping with the early phase of IL 2 mRNA accumulation, suppress IL 2 gene expression induced by PHA as well as TPA, and that antibody 9.6 and CsA exert their inhibitory effect by distinct mechanism(s).

Animals↗
PubMed1986

Promoter region of interleukin-2 gene undergoes chromatin structure changes and confers inducibility on chloramphenicol acetyltransferase gene during activation of T cells.

The chromatin structure of the interleukin-2 (IL-2) gene was probed by DNase I treatment of isolated nuclei. The 5' region of the IL-2 gene contains three regions of hypersensitivity to DNase I. When peripheral blood T cells or Jurkat T cells are stimulated with mitogens, IL-2 message is induced, and the promoter region of the IL-2 gene develops an additional hypersensitive site. This suggests that a DNA sequence close to the transcriptional start site is involved in the transduction of the extracellular signal. Such a conclusion is further supported by DNA transfection experiments. A short segment of DNA, which includes the region of induced hypersensitivity, confers inducibility on the linked chloramphenicol acetyltransferase gene in transiently transfected Jurkat cells. In addition, cells of nonhematopoietic origins exhibit a strikingly different chromatin pattern of IL-2, suggesting a role during differentiation for some of the hypersensitive sites.

Acetyltransferases↗
PubMed1985

Cyclosporine augments receptor-mediated cellular Ca2+ fluxes in isolated hepatocytes.

The immunosuppressive agent, cyclosporine, has been found to augment receptor-stimulated calcium fluxes in isolated hepatocytes. After treatment of Quin 2-loaded hepatocytes with cyclosporine, both the amplitude and duration of the vasopressin-induced rise in the cytosolic free Ca2+ are increased. These effects are dependent upon the concentration and time of exposure of the cells to cyclosporine. Cyclosporine increases both 45Ca2+ influx across the plasma membrane and the cellular calcium content. The total cellular magnesium, sodium, and potassium contents are not affected by cyclosporine. However, cyclosporine treatment, per se, has no apparent effect on the cytosolic free Ca2+ concentration as assayed by Quin 2 fluorescence. The increase in total cell calcium is associated with progressive increases in the calcium content of the endoplasmic reticular and mitochondrial calcium pools. The vasopressin-induced net efflux of Ca2+ from hepatocytes was 2-fold greater after treatment with 10 micrograms/ml cyclosporine for 10 min, but the lag time prior to the onset of Ca2+ efflux was not affected. These results are interpreted on the basis of cyclosporine having a primary effect on increasing the permeability of the plasma membrane to Ca2+, thereby leading to an increase of the calcium content of the hormone-sensitive intracellular calcium pool.

Aminoquinolines↗
PubMed1985

Suppression of interleukin 2 receptor acquisition by monoclonal antibodies recognizing the 50 KD protein associated with the sheep erythrocyte receptor on human T lymphocytes.

Monoclonal antibodies OKT11A, 9.6, and 35.1 recognize epitopes on a 50000 dalton surface molecule (p50) identical to or closely associated with the sheep erythrocyte receptor (E receptor) on human T lymphocytes. These three antibodies were investigated for ability to inhibit T cell proliferation and interleukin 2 (IL 2) receptor acquisition (determined with anti-Tac antibody in an immunofluorescence assay) induced by the lectin mitogen phytohemagglutinin (PHA) or by the phorbol ester 12-O-tetradecanoyl-phorbol-13 acetate (TPA). OKT11A, 9.6, and 35.1 were found to suppress [3H]thymidine incorporation and IL 2 receptor acquisition stimulated by PHA but not by TPA. This inhibition was not attributable to a lag in kinetics, but was sustained throughout 4 to 5 days of culture. Because OKT11A and 9.6 have been reported to suppress lectin mitogen-induced IL 2 production, we attempted to overcome inhibition of proliferation with exogenous IL 2 (MLA144 supernatants or immunoaffinity-purified human IL 2). Adding IL 2 at the initiation of culture abrogated the suppressive effect of all three anti-p50 antibodies on proliferation and on the acquisition of IL 2 receptors, raising the possibility that IL 2 may up-regulate expression of its cellular receptor on human T lymphocytes. These data, together with previous reports, indicate that OKT11A, 9.6, and 35.1 suppress lectin mitogen-induced T cell proliferation by impairing both IL 2 elaboration and IL 2 receptor acquisition, and suggest that IL 2 may be capable, at least under some conditions, of increasing expression of IL 2 receptors on human T lymphocytes.

Animals↗
PubMed1985

Functional properties of the 50 kd protein associated with the E-receptor on human T lymphocytes: suppression of IL 2 production by anti-p50 monoclonal antibodies.

Monoclonal antibody 9.6 is specific for a 50 kd T cell surface protein (p50) associated with the sheep erythrocyte (E)-receptor on human T lymphocytes. This antibody interferes with many T cell functions. We have examined the effect of antibody 9.6 on lymphocyte proliferation and interleukin 2 (IL 2) production triggered by mitogens, soluble antigens, and alloantigens to elucidate the mechanism(s) of its immunosuppressive action. At concentrations as low as 50 ng/ml, 9.6 suppressed lymphocyte proliferation and the elaboration of IL 2 by T cells stimulated by PHA, alloantigens, or low concentrations of the phorbol ester TPA (less than or equal to ng/ml). Furthermore, in cultures stimulated by a combination of PHA plus TPA, 9.6 did not inhibit the acquisition of IL 2 receptors but inhibited proliferation and IL 2 production. Immunoaffinity-purified IL 2 completely restored lymphocyte proliferation in cultures inhibited by 9.6. Studies of kinetics of inhibition by 9.6 showed that this antibody inhibited lymphocyte proliferation induced by PHA, alloantigen, and PPD even when added at 24, 48, and 72 hr, respectively, after the initiation of these cultures, suggesting that 9.6 does not block lectin binding or antigen recognition by T cells and that it can inhibit lymphocyte proliferation even after cells have undergone one or more rounds of cell division. A dose-response analysis of lymphocyte proliferation induced by PHA or by TPA demonstrated that the degree of inhibition by 9.6 decreased with increasing concentrations of these mitogens. Antibody 9.6 did not inhibit lymphocyte response induced by optimal concentrations of PHA (50 to 100 micrograms/ml; PHA-M) but inhibited proliferation of maximally induced lymphocytes by using a synergistic combination of low concentrations of PHA (5 micrograms/ml, PHA-M) plus TPA (1 ng/ml). Taken together, these findings indicate that 1) 9.6 inhibits lymphocyte proliferation by affecting IL 2 production, 2) 9.6 does not inhibit the acquisition of 9.6 receptors induced by a synergistic combination of PHA plus TPA, and 3) p50 molecules may be involved in multiple pathways of T cell activation.

Antibodies, Monoclonal↗
PubMed1983

Human monocyte-histiocyte differentiation antigens identified by monoclonal antibodies.

Two distinct differentiation antigens of human myelomonocytic cells are defined using murine monoclonal antibodies. The antigens recognized by antibodies 20.2 and 20.3 are expressed by all cells of the monocyte lineage in both peripheral blood and bone marrow. Cell-sorting experiments demonstrated that histiocytes and immature bone marrow cells with detectable alpha-naphthyl butyrate esterase activity also express both antigens. Within cells of other lineages, the antigens had distinct patterns of expression. Immature myeloid cells were 20.2 negative, but 20.3 positive; whereas mature myeloid cells were 20.2 positive, but 20.3 negative. Nucleated erythroid cells and platelets expressed only the 20.3 antigen. These results indicate that myeloid and monocytic cells share common differentiation antigens with cells of the erythroid and megakaryocytic lineages. The 20.2 and 20.3 antibodies reacted with the leukemic cells from some patients with acute nonlymphocytic leukemia (FAB, M1-M5) and with some cell lines derived from patients with nonlymphocytic leukemia, but not with blast cells from patients with lymphoid leukemia or with lymphoid leukemic cell lines. These antibodies may prove useful in studying the differentiation of bone marrow stem cells, in defining the cellular origins and classification of leukemias, and in the identification of distinct prognostic subgroups of acute nonlymphocytic leukemia.

Antibodies, Monoclonal↗
PubMed1982

Trachoma therapy with topical tetracycline and oral erythromycin: a comparative trial.

Because topical antibiotic treatment has had a limited effect in previous controlled trials against trachoma, treatment with oral erythromycin was compared with topical tetracycline in 6-8-year-old children in southern Tunisia who had potentially blinding active trachoma. A total of 169 children were divided into two groups that were carefully matched for age, sex, locality, and intensity of disease. Oral erythromycin ethyl succinate in a paediatric dosage form was administered to one group and topical 1% tetracycline ointment to the other group, twice daily, six days a week for three weeks. The two treatments were equivalent in effectiveness and resulted in a substantial decrease in disease intensity and a marked reduction in chlamydial infection detected in conjunctival smears. To maintain blood levels of antibiotics known to be effective in the treatment of chlamydial infections with a dosage schedule possible in a trachoma control programme, one of the long-acting tetracyclines (doxycycline or minocycline) might be considered. Such systemic chemotherapy should be limited to selective treatment of individuals who can be adequately monitored.

Administration, Oral↗
PubMed1981

Identification of a human T lymphocyte surface protein associated with the E-rosette receptor.

We describe a new monoclonal murine antibody that reacts with a 50,000-mol wt polypeptide that appears to be present on all E-rosetting cells. We conclude that this antigen is either identical to or closely associated with the E receptor because of (a) the high degree of concordance between E-rosette formation and 9.6 antigen expression, (b) the inhibition of rosette formation by preincubation of cells with 9.6 antibody, and (c) the observed failure of cells lysostripped of 9.6 antigen to form E-rosettes. This last finding suggests cocapping of 9.6 antigen and the E receptor.

Antigens, Surface↗
PubMed1981

A supertypic HLA-DR specificity (DR4+5) defined by murine monoclonal antibody.

The hybridoma technique was used to produce a monoclonal antibody specific for a polymorphic determinant on human la antigens. BALB/c mice were immunized with a B-lymphoblastoid cell line derived from an HLA-DR3/DR4 positive donor. Hybridoma culture supernates were screened in two stages by means of the microcytotoxicity assay. Supernates were first tested against the la-positive immunizing cell line and against la-negative cells. Cultures identified as producing antibody cytoxic for the immunizing cell line but not for la-negative cells were subcultured and the supernates then tested against a selected panel of HLA-D homozygous cell lines (HCL). In this manner, it was possible to identify a microwell of hybrid cells producing an antibody that reacted with a polymorphic HLA-DR determinant. Cells from this culture, designated 17.15, were cloned twice by limiting dilution. Specificity was evaluated with a panel of 39 HCL and B cells from 70 normal donors. Antibody 17.15 recognized a supertypic DR "4 + 5" specificity, which was also present on DRw9 and some DR7 positive cells. These findings suggest that the cross-reactivity groups DR "4 + 5" (MB-3) and DR "4 + 7" (MT-3) defined by alloantisera may share a common supertypic specificity that is recognized by monoclonal antibody 17.15.

Animals↗
PubMed1981

A novel human T cell antigen preferentially expressed on mature T cells and shared by both well and poorly differentiated B cell leukemias and lymphomas.

A new lymphocyte differentiation antigen shared by all normal T cells and some malignant B cells was defined by a monoclonal antibody designated 12.1. This antibody reacted with all peripheral blood T cells but not with normal B cells and B cell lines. Analysis with a fluorescence activated cell sorter showed that the expression of 12.1 antigen changes during T cell maturation. Most thymocytes, blasts of acute T cell leukemia, and cells from established leukemic T cell lines bear a small amount of 12.1 antigen. In contrast the majority of peripheral blood T cells, activated T cells, and leukemic T cells of the Sezary syndrome bear a large amount of 12.1 antigen. Unexpectedly, antibody 12.1 reacted with leukemic cells from most patients with B-type chronic lymphocytic leukemia (CLL) and some patients with lymphosarcoma cell leukemia (LSCL). Among these leukemias, expression of the 12.1 antigen was not correlated with the stage of B cell maturation, with the amount of surface immunoglobulin on the cells, or with the presence or absence of monoclonal gammapathy. In a comparative serologic analysis the antigen defined by antibody 12.1 was distinct from the p67 T cell antigen (defined by monoclonal antibody 10.2) that is also known to be expressed by B-type CLL cells.

Acute Disease↗