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Biomedical subjects

Y Jacques

Publications and source records attributed to Y Jacques.

At least 91 records · Page 5Linked to original sources
PubMed1989

Response of murine IL3-sensitive cell lines to cytokines of human and murine origin.

We analyzed the proliferative response of DA1, DA1-a, NFS 60, 32DC1, Ea 3-17 and FDCP2 murine interleukin 3 (mIL3)-sensitive cell lines to human recombinant IL1 alpha, IL1 beta, IL2, IL4, IL5, IL6, granulocyte-CSF (G-CSF), macrophage-CSF (M-CSF), granulocyte-macrophage-CSF (GM-CSF), interferon gamma (IFN gamma), tumor necrosis factor (TNF) alpha, gibbon IL3, purified HILDA and mouse recombinant IL3, IL4, GM-CSF. All cell lines responded to mIL3 and IL4. Various response patterns were observed with human IL2, G-CSF and murine GM-CSF. Human IL4 and GM-CSF were absolutely inefficient in triggering proliferation of lines sensitive to their murine counterparts, confirming the species specificity of these two cytokines. Among the cell lines responding to G-CSF, some variations in sensitivities were observed. Thus the 32DC1 cell line needed 10 to 30 times more G-CSF to reach the same level of proliferation as the NFS60 cell line. DA1-a was the only factor-dependent cell line responding to purified HILDA, and IL6 was found to trigger proliferation of the NFS60 cell line, with a half-maximum effect observed for 0.1 pM of hormone.

Animals↗
PubMed1988

A study on OX39, a murine anti-rat interleukin 2 receptor antibody. A report on receptor binding and effects on allograft survival.

OX39, a murine IgG1 monoclonal antibody (MoAb) that recognizes the 55 kDa alpha chain of the rat interleukin 2 receptor (R-IL2), was studied in vitro for its ability to interfere with IL2 binding and IL2-induced proliferation on rat concanavalin A (ConA) blasts and in vivo in a model of rat heart allografts. In vitro studies indicated that OX39 MoAb interacts with a single class of sites on the alpha chain of the rat R-IL2 with a high affinity (KD = 0.8 nm) and competes with IL2 binding on this chain (KI = 0.53 nm). In contrast, OX39 MoAb was found to be 10-20 times less efficient in competing with IL2 binding to the high-affinity R-IL2 (KI approximately 10 nm). It is proposed that the epitope recognized by OX39 on the alpha chain (low-affinity R-IL2) is modified on (or buried in) the high-affinity R-IL2 configuration. Accordingly, OX39 was found to be a weak inhibitor in vitro on IL2-induced proliferation and in vivo on allograft rejection. Allograft survival was unaffected by doses of OX39 of 20 and 50 micrograms/rat for 9 days; only a borderline effect was noted when doses as high as 250 micrograms/rat were used. A significant, but restricted, effect of OX39 could be further detected when combined with low doses of cyclosporine A (1.5 mg/kg), which were ineffective by themselves. Together, our data suggest that in order to be efficient in vivo, anti-R-IL2 MoAbs must bind with high affinity to epitopes involved in the high-affinity IL2 binding site.

Animals↗
PubMed1988

Prophylactic use of a monoclonal antibody (33B3.1) directed against interleukin 2 receptor following human renal transplantation.

33B3.1, a rat IgG2a monoclonal antibody (MAb) directed against interleukin 2 receptor, has been given in association with prednisone and azathioprine to prevent rejection in 30 recipients of a primary cadaveric kidney transplant. The MAb 33B3.1 had been administered intravenously (IV) at 10 mg per day for 2 weeks. Clinical and biological tolerance were excellent. Only one patient had a rejection episode (reversible) during the MAb treatment period. These results were significantly better than those recorded from a historical group of patients that received only prednisone and azathioprine, and were similar to those from patients who received antithymocyte globulin instead of 33B3.1. There was no life threatening infectious episode and all patients are alive. Ninety-seven percent of the patients have a functional graft (follow-up, 30 to 210 days). Enzyme-linked immunosorbent assay (ELISA) of 33B3.1 indicate that circulating trough blood level peaked at day 6 (30 nm). The majority of patients (85%) developed either IgG or IgM antibodies with a maximal response at day 24 for both isotypes. We conclude that this new treatment that targets a functional receptor present on activated lymphocytes only, is well tolerated and highly efficient in preventing early rejection after human renal transplantation.

Animals↗
PubMed1988

Biochemical characterization and purification of HILDA, a human lymphokine active on eosinophils and bone marrow cells.

We previously described a lymphokine termed HILDA (for human interleukin DA) produced by T-lymphocyte alloreactive clones after antigenic stimulation. This factor sustains the growth of a murine IL3-sensitive cell line (DA2). In addition, HILDA is a potent activator of eosinophils and displays a burst-promoting activity on human bone marrow. In the present study, HILDA was purified to homogeneity from T-cell clone supernatant using successively sequential concentration, concanavalin A (ConA) affinity chromatography with differential elution (alpha-D glucopyranoside and alpha-D mannopyranoside), high-performance liquid chromatography (HPLC) gel filtration and reverse-phase HPLC. The pure material appeared as a 38-kd glycoprotein on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) under reducing or nonreducing conditions. Biologic activity could be recovered from SDS-PAGE gel slices corresponding to the 38-kd band. We conclude from the specificity of the DA-2 cell line and biochemical characteristics described that this lymphokine is different from other known factors produced by human T lymphocytes.

Biological Assay↗
PubMed1987

A soluble interleukin 2 receptor produced by a normal alloreactive human T cell clone binds interleukin 2 with low affinity.

Several alloreactive human T cell clones derived from a rejected kidney graft were found to produce in their culture supernatants soluble interleukin 2 receptors (IL-2R) upon specific antigenic challenge (irradiated B cell line from the graft's donor). Among them, the 2B11, a high producer clone, was used to purify a soluble IL-2R preparation which was analyzed, in comparison with the high and low affinity cell-surface IL-2R expressed by 2B11 cells, for its parameters of interaction with a set of anti-IL-2R monoclonal antibodies (mAb) and IL-2. This soluble receptor purified by affinity chromatography (anti-IL-2R mAb column) and sodium dodecyl sulfate gel electrophoresis is composed of a single chain of 35,000 to 45,000 Da. Immunoradiometric assays (IRMA) at equilibrium were set up, using pairs of mAb directed against two separate epitopes on the Tac antigen of the human IL-2R, to measure the respective dissociation constant of these mAb for the soluble IL-2R. They were found to be identical to those found on the cell-surface IL-2R. A 1:1 stoichiometry between the two epitopes were found both on the membrane and soluble species. Competition experiments between membrane and soluble IL-2R for binding the mAb allowed the quantitative analysis of the concentration of soluble IL-2R without the need of amino acid analysis on purified material and set up a quantitative IRMA for the human soluble IL-2R (detection limit 5 pM). The affinity of the soluble IL-2R for IL-2 was determined by various techniques including an IRMA using an anti-IL-2R mAb and radiolabeled IL-2. The results obtained led us to conclude that the soluble IL-2R binds IL-2 with a dissociation constant (KD = 30 nM) identical to that found for the binding of IL-2 to low affinity cell-surface IL-2R (Tac antigen). Whereas 2.5% of cell-surface IL-2R expressed 2 days after antigenic stimulation of 2B11 cells were of high affinity for IL-2 (KD = 25 pM), no (less than 0.07%) high affinity binding sites could be detected on the purified soluble IL-2R. This soluble IL-2R therefore likely corresponds to a truncated, extracellular part of the membrane Tac antigen. The amounts of soluble Tac antigen produced by the 2B11 alloreactive human T cell clone did not exceed 1 nM and, as expected from the binding studies, did not affect IL-2-induced T cell proliferation. The physiologic and pathologic implications of our results are discussed.

Antibodies, Monoclonal↗
PubMed1987

Prevention of rejection of kidney transplants by monoclonal antibody directed against interleukin 2.

The effect of 33B3.1, a rat IgG2a monoclonal antibody (MAb) directed against interleukin 2 receptors on activated T lymphocytes, was studied during the first two weeks after transplantation in an attempt to prevent rejection in primary, cadaveric, kidney transplant recipients. 9 patients received 5 mg 33B3.1 daily by intravenous infusion for 14 days (group A) and 18 received 10 mg daily (group B). Both groups also received prednisone and azathioprine. In threatened rejection, rescue treatment consisted of anti-thymocyte globulin (ATG). 33B3.1 was well tolerated, with mild fever during the first 2 days being the most common side-effect. 3 patients in group A had a reversible acute rejection episode before day 14, whereas only 1 patient in group B had reversible rejection. 20 of 30 historical control patients (prednisone/azathioprine) and 2 of 55 patients previously treated with ATG had a rejection episode in a similar period after transplantation. Trough levels of 33B3.1 in the blood ranged from undetectable to 1.6 micrograms/ml in group A and from 0.3 to 9 micrograms/ml in group B. Most patients had antibodies against 33B3.1 by the end of treatment.

Acute Disease↗
PubMed1987

Parameters of interaction of a novel monoclonal antibody (33B3.1) with the human IL2-receptors: interrelationship between 33B3.1, anti-Tac, and IL2 binding sites.

This report describes the molecular parameters of interaction of a new antibody (33B3.1) with the human membrane RIL2 expressed by ConA-activated T lymphocytes or allogeneic T-cell clones established from a rejected kidney allograft: the 33B3.1 immunoprecipitates a membrane protein of 55000 MW. It inhibits IL2-driven proliferation of activated T cells. This inhibition occurred in the nanomolar range when low concentrations of recombinant IL2 (rec-IL2) were used. The (125I)-33B3.1 binds in a specific way to a single class of receptor sites on activated T cells. The rate constants of association and dissociation at 37 degrees C of the labeled 33B3.1 were k*1 = 12 X 10(5) M-1 s-1 and k*-1 = 7 X 10(-4) s-1, respectively, and its equilibrium dissociation constant was KD = 0.65 nM. Maximal binding capacities were fairly variable among T-cell clones, as high as 300,000 sites/cell for some of them. Competition experiments demonstrate that the 33B3.1 and anti-Tac interact with the RIL2 in a competitive manner, suggesting that they recognize closely associated epitopes on the RIL2. However, the 33B3.1 inhibits the binding of (35S)-recombinant IL2 to its high affinity RIL2 in a noncompetitive way. The 33B3.1 seems therefore to interact with an epitope close but distinct from the IL2 binding site. Our data could suggest either that the 33B3.1 is able to convert high affinity RIL2 towards low affinity conformations or that there is more than one IL2 binding site per molecule of high affinity RIL2.

Antibodies, Monoclonal↗