Several studies have demonstrated the existence of a murine NK1.1+ alphabeta T cell subset expres... more Several studies have demonstrated the existence of a murine NK1.1+ alphabeta T cell subset expressing V alpha14+ TCR alpha-chains with highly conserved invariant junctional sequences and able to secrete Th2 cytokines when exposed to CD1+ stimulator cells. In humans, alphabeta T cells carrying invariant V alpha24+ TCR alpha-chains highly homologous to those expressed by murine NK1.1 cells have been recently described. Here we show that these cells (referred to as V alpha24inv T cells) and murine NK1.1+ alphabeta T cells resemble each other in several ways. First, like their murine counterparts, T cells expressing high levels of V alpha24inv TCRs can be either CD4- CD8- double negative (DN) or CD4+, but they never express heterodimeric CD8 molecules. Second, most V alpha24inv T cells are brightly stained by NKRP1-specific mAb but not by mAb directed against other type II transmembrane proteins of the NK complex. Third, DN and particularly CD4+ V alpha24inv T cells are greatly enriched...
Several alloreactive human T cell clones derived from a rejected kidney graft were found to produ... more 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...
The action potential Na+ ionophore of excitable cells can be activated either by alkaloid compoun... more The action potential Na+ ionophore of excitable cells can be activated either by alkaloid compounds such as veratridine, or by small polypeptide toxins extracted from scorpion venom or sea anemone1,2. One of the main features of this Na+ channel is that it is blocked by tetrodotoxin (TTX). However, we report here that during analysis of Na+ influx in resting fibroblasts,
blast, another mesenchymal cell lineage, was found to The high-affinity receptor for interleukin-... more blast, another mesenchymal cell lineage, was found to The high-affinity receptor for interleukin-11 (IL-11) be a source of IL-11 (Paul et al., 1990; Elias et al., 1995). is composed of two subunits, IL-11 receptor a chain The spectrum of biological activities of IL-11 overlaps (IL-11Ra) and gp130, the common subunit of the inwith that of interleukin-6 (IL-6): IL-11 acts on erythterleukin-6 (IL-6), ciliary neurotrophic factor (CNTF), ropoiesis (Quesniaux et al., 1992), megakaryocytosis leukemia inhibitory factor, and oncostatin M recep-(Bruno et al., 1991), and B-lymphocyte maturation (Yin tors. The IL-11 receptor-specific a chain shares homolet al., 1992). Outside the lymphohematopoietic system, ogies with the a chain of the CNTF and IL-6 receptors. IL-11, like IL-6, stimulates adipogenesis (Baumann We isolated and characterized genomic DNA clones enand Schendel, 1991) and regulates neuronal differenticompassing the entire coding sequence of the IL-11Ra ation (Mehler et al., 1993). Recent data suggest that cDNA. The exon-intron organization of the IL-11R unlike IL-6, IL-11 plays a hierarchically central role in gene (HGMW-approved symbol IL11RA) is consistent osteoclast formation (Girasole et al., 1994). with the predicted structure of the different domains IL-11 exerts its biological activities through a twoof the IL-11Ra protein, confirming evolutionary concomponent receptor complex (Hilton et al., 1994). ILservation at the level of gene organization among the 11 requires a specific receptor component identified as hematopoietic cytokine receptor family. The IL-11R the IL-11 receptor a chain (IL-11Ra) (Hilton et al., gene has been assigned to chromosome 9 band p13 by 1994) in addition to the gp130 signal transducer subin situ hybridization using human IL-11Ra cDNA as a probe. The fact that the ciliary neurotrophic factor unit, which is shared by a family of cytokines including (CNTFR) gene has recently been localized on this same IL-6, ciliary neurotrophic factor (CNTF), leukemia inband and the conserved genomic structure between hibitory factor, and oncostatin M. IL-11R and CNTFR suggest that they may have evolved We have recently cloned the human IL-11Ra chain from a common ancestor. ᭧ 1996 Academic Press, Inc. and shown that it is present in two isoforms, IL-11Ra 1 and IL-11Ra 2 (Chérel et al., 1995). IL-11Ra 1 has a small intracytoplasmic domain comparable to that of
We thank Dr B. Strickland for doing and reporting the computed tomography scans and Mr Christophe... more We thank Dr B. Strickland for doing and reporting the computed tomography scans and Mr Christopher Freemantle for doing the whole-body counting. D. C. C. and D. P. D. were supported by Chest, Heart and Stroke Association, A. M. P. and S. H. S. by Wellcome Trust, S. G. N. by the Nuffield Foundation, and P. G. by Bencard. "'In was kindly supplied by Amersham International plc.
The receptor for the cytokine leukemia inhibitory factor (LIF) associates the low affinity bindin... more The receptor for the cytokine leukemia inhibitory factor (LIF) associates the low affinity binding component gp190 and the high affinity converter gp130, both of which are members of the family of hematopoietic receptors characterized by the cytokine receptor homology (CRH) domain. The gp190 is among the very few members of this large family to contain two CRH domains. The membrane-distal one (herein called D1) is followed by an Ig-like domain, a membrane-proximal CRH domain called D2, and three type III fibronectin repeats. We raised a series of monoclonal antibodies specific for the human gp190. Among them was the blocking antibody 1C7, which was directed against the D1Ig region and which impaired the binding of LIF to gp190. Another blocking antibody, called 12D3, was directed against domain D2 and interfered with the reconstitution of the high affinity receptor complex, independently of the interaction between LIF and gp190. The blocking effect of these two antibodies concerned ...
Cellular and molecular biology (Noisy-le-Grand, France), 2001
Human interleukin-2 (IL-2) interacts with two types of functional receptors (IL-2R alpha betagamm... more Human interleukin-2 (IL-2) interacts with two types of functional receptors (IL-2R alpha betagamma and IL-2R betagamma) and acts on a broad range of target cells involved in inflammatory reactions and immune responses. IL-2 is also used in different clinical trials aimed at improving the treatment of some cancers and the recovery of CD4 lymphocytes by HIV patients. The therapeutic index of IL-2 is limited by various side effects dominated by the vascular leak syndrome. We have shown that a chemically synthesised fragment of the IL-2 sequence can fold into a helical tetramer likely mimicking the quatemary structure of an hemopoietin. Indeed, peptide p1-30 (containing amino acids 1 to 30, including the sequence corresponding to the entire alpha helix A of IL-2) spontaneously folds into an alpha-helical homotetramer and stimulates the growth of T-cell lines expressing human IL-2R beta, whereas shorter versions of the peptide lack helical structure and are inactive. At the cellular leve...
The role of heterotrimeric G proteins in T-cell activation is poorly understood. Here we show tha... more The role of heterotrimeric G proteins in T-cell activation is poorly understood. Here we show that in normal, mature human T-cells, expression of G alpha16, the 43 kDa alpha subunit of G16, varies widely, depending on T-cell activation status. Quiescent blood lymphocytes strongly up-regulate G alpha16 after Leuco A stimulation: protein expression of G alpha16 is maximal at day 4, then decreases. Consistently, in human T-cell clones, expression of G alpha16 is high in the first week following activation and decreases rapidly within the second week. In addition, permanent disruption of regulated G alpha16 expression in Jurkat T-cells by stable overexpression of 43 kDa G alpha16 inhibited Leuco A-induced interleukin-2 production, CD69 up-regulation and cell apoptosis (by 58%, 46% and 74%, respectively), suggesting that coordinate regulation of G alpha16 expression is necessary for optimal activation-induced T-cell responses, and that G alpha16 proteins may be involved in the negative r...
The availability of soluble forms of T-cell antigen receptors (sTCR) should be of great use in th... more The availability of soluble forms of T-cell antigen receptors (sTCR) should be of great use in the detailed characterization of their interactions with ligands, for the generation of anti-TCR monoclonal antibodies (mAb), and for the eventual determination of their three-dimensional structures by x-ray crystallography. Here, we show that efficient secretion of nonchimeric disulfide-linked human gamma delta TCR could be achieved by simply introducing translational termination codons upstream from the sequences encoding TCR chain transmembrane regions. This recombinant protein appeared to be correctly folded, as judged by its reactivity with a panel of anti-gamma and anti-delta mAbs, and proved to be a powerful immunogen, allowing generation of mAb that are able to recognize both soluble- and membrane-bound gamma delta TCR. While variable and constant domains of gamma delta sTCR seem to be folded into compact conformations, the extreme sensitivity of its interchain disulfide bridge to ...
Interleukin-11 (IL-11) is a stromal cell-derived cytokine with multiple biologic activities on ly... more Interleukin-11 (IL-11) is a stromal cell-derived cytokine with multiple biologic activities on lymphohematopoietic cells. It belongs to a family of pleiotropic and redundant cytokines that use the gp 130 transducing subunit in their high affinity receptors. By amplifying human cDNA libraries with oligonucleotide primers corresponding to the conserved WSXWS motif found in the hematopoietic cytokine receptor family, a novel cytokine receptor cDNA was identified that, based on high (82%) sequence homology with the recently cloned murine IL-11 receptor, appears to encode the human IL-11 receptor. This receptor is a 422-amino acid protein containing a signal peptide followed by extracellular, transmembrane, and cytoplasmic domains. The extracellular region has a two-domain structure homologous to those of the IL-6 and ciliary neurotrophic factor (CNTF) receptors: an immunoglobulin-like domain and a cytokine receptor-like domain. In addition, an isoform of the human IL-11 receptor that la...
American journal of kidney diseases : the official journal of the National Kidney Foundation, 1988
33B3.1, a rat IgG2a monoclonal antibody (MAb) directed against interleukin 2 receptor, has been g... more 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 ...
The interaction of a series of pyrethroids with the Na+ channel of mouse neuroblastoma cells has ... more The interaction of a series of pyrethroids with the Na+ channel of mouse neuroblastoma cells has been followed using both an electrophysiological and a 22 Na+ influx approach. By themselves, pyrethroids do not stimulate 22 Na+ entry through the ...
Osteoclastic cells from giant cell tumour of bone (GCT) of bone provide a rich source for investi... more Osteoclastic cells from giant cell tumour of bone (GCT) of bone provide a rich source for investigation of cellular mechanisms leading to formation of multinucleated cells, the resorption process and involvement of hormones and cytokines in these events. In the present study we investigated the effect of 1,25-dihydroxyvitamin D3 (VD3) and leukaemia inhibitory factor (LIF) on the resorbing potential of osteoclast of GCT origin using quantitative image-analysis of resorption lacunae in an in vitro dentine model. While VD3 unsignificantly increased the number of resorption pits and implicated surface after 7 days of GCT cell culturing, the stimulative effect of LIF was statistically significant. In cultures supplemented with LIF (5000 U/ml) the number of lacunae and resorption surface increased by 38% and 55%, respectively, when compared with control cultures. We suggest that both osteotropic agents increased osteoclastic activity, as the number of multinucleated cells was similar in control and experimental cultures. Seeding of GCT cells on biphasic calcium phosphate substratum revealed the relative inability of osteoclastic cells to resorb this synthetic material.
Monoclonal antibodies directed against the P55 component of the interleukin 2 receptor (IL-2-R) h... more Monoclonal antibodies directed against the P55 component of the interleukin 2 receptor (IL-2-R) have been used to prevent allograft rejection in various animal models, including primates and man. This study compares the functional effects of seven MoAbs directed against the mouse IL-2-R P55 chain both in vitro using the mouse CTL-L2 cell line and in vivo in a sheep red blood cell-induced delayed-type hypersensitivity model. Data from in vitro studies showed that a cluster of four MoAbs (cluster I: 5A2, 125, 135 [IgG2a] and AMT13 [IgG2b]) competed with IL-2 for binding to the P55 chain and caused an inhibition of IL-2-induced proliferation on CTL-L2. The respective dissociation constants (Kd) of the four MoAbs were 1.1, 1.4, 2.5, and 5.5 nM, and they all displayed a common maximal binding capacity of 2 x 10(5) sites per cell on CTL-L2. None of these MoAbs were found to fix rabbit complement. The three other MoAbs (2E4: IgG2a, 7D4: IgM, PC61: IgG1) with respective Kd of 0.8, 0.2, and 0.85 nM and maximal binding capacities of 2 x 10(5), 4 x 10(5) sites per cell did not interfere with IL-2 binding and did not affect the IL-2-induced proliferation of the murine cell line. All three MoAbs were found to define three separate epitopic clusters independent of cluster I. Among them, only 2E4 induced a strong complement-mediated cytotoxicity. In vivo experiments showed that all MoAbs from cluster I were efficient in suppressing the DTH reaction and that the magnitude of their effect was consistent with their respective Kds. At a suboptimal dose of 1 microgram per day, the DTH inhibition indices were 40%, 43%, 23%, and 9% for 5A2, 125, 135, and AMT13, respectively. The 2E4 MoAb was found to be as efficient as cluster I MoAbs in suppressing DTH (53% inhibition at 1 microgram/day) while 7D4 and PC61 induced only a moderate inhibitory effect (37% inhibition for each MoAb given at 10 micrograms/day, compared with 70% inhibition for cluster I MoAbs). Taken together, our results indicate that blocking the IL-2/IL-2-R interaction without complement fixation is sufficient per se to attenuate the DTH reaction, and conversely that strong complement-mediated cytotoxicity in the absence of a functional effect in the IL-2/IL-2-R interaction is also effective in this system. Finally, no synergistic effect between MoAbs belonging to different clusters was evidenced in the DTH model.
Several studies have demonstrated the existence of a murine NK1.1+ alphabeta T cell subset expres... more Several studies have demonstrated the existence of a murine NK1.1+ alphabeta T cell subset expressing V alpha14+ TCR alpha-chains with highly conserved invariant junctional sequences and able to secrete Th2 cytokines when exposed to CD1+ stimulator cells. In humans, alphabeta T cells carrying invariant V alpha24+ TCR alpha-chains highly homologous to those expressed by murine NK1.1 cells have been recently described. Here we show that these cells (referred to as V alpha24inv T cells) and murine NK1.1+ alphabeta T cells resemble each other in several ways. First, like their murine counterparts, T cells expressing high levels of V alpha24inv TCRs can be either CD4- CD8- double negative (DN) or CD4+, but they never express heterodimeric CD8 molecules. Second, most V alpha24inv T cells are brightly stained by NKRP1-specific mAb but not by mAb directed against other type II transmembrane proteins of the NK complex. Third, DN and particularly CD4+ V alpha24inv T cells are greatly enriched...
Several alloreactive human T cell clones derived from a rejected kidney graft were found to produ... more 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...
The action potential Na+ ionophore of excitable cells can be activated either by alkaloid compoun... more The action potential Na+ ionophore of excitable cells can be activated either by alkaloid compounds such as veratridine, or by small polypeptide toxins extracted from scorpion venom or sea anemone1,2. One of the main features of this Na+ channel is that it is blocked by tetrodotoxin (TTX). However, we report here that during analysis of Na+ influx in resting fibroblasts,
blast, another mesenchymal cell lineage, was found to The high-affinity receptor for interleukin-... more blast, another mesenchymal cell lineage, was found to The high-affinity receptor for interleukin-11 (IL-11) be a source of IL-11 (Paul et al., 1990; Elias et al., 1995). is composed of two subunits, IL-11 receptor a chain The spectrum of biological activities of IL-11 overlaps (IL-11Ra) and gp130, the common subunit of the inwith that of interleukin-6 (IL-6): IL-11 acts on erythterleukin-6 (IL-6), ciliary neurotrophic factor (CNTF), ropoiesis (Quesniaux et al., 1992), megakaryocytosis leukemia inhibitory factor, and oncostatin M recep-(Bruno et al., 1991), and B-lymphocyte maturation (Yin tors. The IL-11 receptor-specific a chain shares homolet al., 1992). Outside the lymphohematopoietic system, ogies with the a chain of the CNTF and IL-6 receptors. IL-11, like IL-6, stimulates adipogenesis (Baumann We isolated and characterized genomic DNA clones enand Schendel, 1991) and regulates neuronal differenticompassing the entire coding sequence of the IL-11Ra ation (Mehler et al., 1993). Recent data suggest that cDNA. The exon-intron organization of the IL-11R unlike IL-6, IL-11 plays a hierarchically central role in gene (HGMW-approved symbol IL11RA) is consistent osteoclast formation (Girasole et al., 1994). with the predicted structure of the different domains IL-11 exerts its biological activities through a twoof the IL-11Ra protein, confirming evolutionary concomponent receptor complex (Hilton et al., 1994). ILservation at the level of gene organization among the 11 requires a specific receptor component identified as hematopoietic cytokine receptor family. The IL-11R the IL-11 receptor a chain (IL-11Ra) (Hilton et al., gene has been assigned to chromosome 9 band p13 by 1994) in addition to the gp130 signal transducer subin situ hybridization using human IL-11Ra cDNA as a probe. The fact that the ciliary neurotrophic factor unit, which is shared by a family of cytokines including (CNTFR) gene has recently been localized on this same IL-6, ciliary neurotrophic factor (CNTF), leukemia inband and the conserved genomic structure between hibitory factor, and oncostatin M. IL-11R and CNTFR suggest that they may have evolved We have recently cloned the human IL-11Ra chain from a common ancestor. ᭧ 1996 Academic Press, Inc. and shown that it is present in two isoforms, IL-11Ra 1 and IL-11Ra 2 (Chérel et al., 1995). IL-11Ra 1 has a small intracytoplasmic domain comparable to that of
We thank Dr B. Strickland for doing and reporting the computed tomography scans and Mr Christophe... more We thank Dr B. Strickland for doing and reporting the computed tomography scans and Mr Christopher Freemantle for doing the whole-body counting. D. C. C. and D. P. D. were supported by Chest, Heart and Stroke Association, A. M. P. and S. H. S. by Wellcome Trust, S. G. N. by the Nuffield Foundation, and P. G. by Bencard. "'In was kindly supplied by Amersham International plc.
The receptor for the cytokine leukemia inhibitory factor (LIF) associates the low affinity bindin... more The receptor for the cytokine leukemia inhibitory factor (LIF) associates the low affinity binding component gp190 and the high affinity converter gp130, both of which are members of the family of hematopoietic receptors characterized by the cytokine receptor homology (CRH) domain. The gp190 is among the very few members of this large family to contain two CRH domains. The membrane-distal one (herein called D1) is followed by an Ig-like domain, a membrane-proximal CRH domain called D2, and three type III fibronectin repeats. We raised a series of monoclonal antibodies specific for the human gp190. Among them was the blocking antibody 1C7, which was directed against the D1Ig region and which impaired the binding of LIF to gp190. Another blocking antibody, called 12D3, was directed against domain D2 and interfered with the reconstitution of the high affinity receptor complex, independently of the interaction between LIF and gp190. The blocking effect of these two antibodies concerned ...
Cellular and molecular biology (Noisy-le-Grand, France), 2001
Human interleukin-2 (IL-2) interacts with two types of functional receptors (IL-2R alpha betagamm... more Human interleukin-2 (IL-2) interacts with two types of functional receptors (IL-2R alpha betagamma and IL-2R betagamma) and acts on a broad range of target cells involved in inflammatory reactions and immune responses. IL-2 is also used in different clinical trials aimed at improving the treatment of some cancers and the recovery of CD4 lymphocytes by HIV patients. The therapeutic index of IL-2 is limited by various side effects dominated by the vascular leak syndrome. We have shown that a chemically synthesised fragment of the IL-2 sequence can fold into a helical tetramer likely mimicking the quatemary structure of an hemopoietin. Indeed, peptide p1-30 (containing amino acids 1 to 30, including the sequence corresponding to the entire alpha helix A of IL-2) spontaneously folds into an alpha-helical homotetramer and stimulates the growth of T-cell lines expressing human IL-2R beta, whereas shorter versions of the peptide lack helical structure and are inactive. At the cellular leve...
The role of heterotrimeric G proteins in T-cell activation is poorly understood. Here we show tha... more The role of heterotrimeric G proteins in T-cell activation is poorly understood. Here we show that in normal, mature human T-cells, expression of G alpha16, the 43 kDa alpha subunit of G16, varies widely, depending on T-cell activation status. Quiescent blood lymphocytes strongly up-regulate G alpha16 after Leuco A stimulation: protein expression of G alpha16 is maximal at day 4, then decreases. Consistently, in human T-cell clones, expression of G alpha16 is high in the first week following activation and decreases rapidly within the second week. In addition, permanent disruption of regulated G alpha16 expression in Jurkat T-cells by stable overexpression of 43 kDa G alpha16 inhibited Leuco A-induced interleukin-2 production, CD69 up-regulation and cell apoptosis (by 58%, 46% and 74%, respectively), suggesting that coordinate regulation of G alpha16 expression is necessary for optimal activation-induced T-cell responses, and that G alpha16 proteins may be involved in the negative r...
The availability of soluble forms of T-cell antigen receptors (sTCR) should be of great use in th... more The availability of soluble forms of T-cell antigen receptors (sTCR) should be of great use in the detailed characterization of their interactions with ligands, for the generation of anti-TCR monoclonal antibodies (mAb), and for the eventual determination of their three-dimensional structures by x-ray crystallography. Here, we show that efficient secretion of nonchimeric disulfide-linked human gamma delta TCR could be achieved by simply introducing translational termination codons upstream from the sequences encoding TCR chain transmembrane regions. This recombinant protein appeared to be correctly folded, as judged by its reactivity with a panel of anti-gamma and anti-delta mAbs, and proved to be a powerful immunogen, allowing generation of mAb that are able to recognize both soluble- and membrane-bound gamma delta TCR. While variable and constant domains of gamma delta sTCR seem to be folded into compact conformations, the extreme sensitivity of its interchain disulfide bridge to ...
Interleukin-11 (IL-11) is a stromal cell-derived cytokine with multiple biologic activities on ly... more Interleukin-11 (IL-11) is a stromal cell-derived cytokine with multiple biologic activities on lymphohematopoietic cells. It belongs to a family of pleiotropic and redundant cytokines that use the gp 130 transducing subunit in their high affinity receptors. By amplifying human cDNA libraries with oligonucleotide primers corresponding to the conserved WSXWS motif found in the hematopoietic cytokine receptor family, a novel cytokine receptor cDNA was identified that, based on high (82%) sequence homology with the recently cloned murine IL-11 receptor, appears to encode the human IL-11 receptor. This receptor is a 422-amino acid protein containing a signal peptide followed by extracellular, transmembrane, and cytoplasmic domains. The extracellular region has a two-domain structure homologous to those of the IL-6 and ciliary neurotrophic factor (CNTF) receptors: an immunoglobulin-like domain and a cytokine receptor-like domain. In addition, an isoform of the human IL-11 receptor that la...
American journal of kidney diseases : the official journal of the National Kidney Foundation, 1988
33B3.1, a rat IgG2a monoclonal antibody (MAb) directed against interleukin 2 receptor, has been g... more 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 ...
The interaction of a series of pyrethroids with the Na+ channel of mouse neuroblastoma cells has ... more The interaction of a series of pyrethroids with the Na+ channel of mouse neuroblastoma cells has been followed using both an electrophysiological and a 22 Na+ influx approach. By themselves, pyrethroids do not stimulate 22 Na+ entry through the ...
Osteoclastic cells from giant cell tumour of bone (GCT) of bone provide a rich source for investi... more Osteoclastic cells from giant cell tumour of bone (GCT) of bone provide a rich source for investigation of cellular mechanisms leading to formation of multinucleated cells, the resorption process and involvement of hormones and cytokines in these events. In the present study we investigated the effect of 1,25-dihydroxyvitamin D3 (VD3) and leukaemia inhibitory factor (LIF) on the resorbing potential of osteoclast of GCT origin using quantitative image-analysis of resorption lacunae in an in vitro dentine model. While VD3 unsignificantly increased the number of resorption pits and implicated surface after 7 days of GCT cell culturing, the stimulative effect of LIF was statistically significant. In cultures supplemented with LIF (5000 U/ml) the number of lacunae and resorption surface increased by 38% and 55%, respectively, when compared with control cultures. We suggest that both osteotropic agents increased osteoclastic activity, as the number of multinucleated cells was similar in control and experimental cultures. Seeding of GCT cells on biphasic calcium phosphate substratum revealed the relative inability of osteoclastic cells to resorb this synthetic material.
Monoclonal antibodies directed against the P55 component of the interleukin 2 receptor (IL-2-R) h... more Monoclonal antibodies directed against the P55 component of the interleukin 2 receptor (IL-2-R) have been used to prevent allograft rejection in various animal models, including primates and man. This study compares the functional effects of seven MoAbs directed against the mouse IL-2-R P55 chain both in vitro using the mouse CTL-L2 cell line and in vivo in a sheep red blood cell-induced delayed-type hypersensitivity model. Data from in vitro studies showed that a cluster of four MoAbs (cluster I: 5A2, 125, 135 [IgG2a] and AMT13 [IgG2b]) competed with IL-2 for binding to the P55 chain and caused an inhibition of IL-2-induced proliferation on CTL-L2. The respective dissociation constants (Kd) of the four MoAbs were 1.1, 1.4, 2.5, and 5.5 nM, and they all displayed a common maximal binding capacity of 2 x 10(5) sites per cell on CTL-L2. None of these MoAbs were found to fix rabbit complement. The three other MoAbs (2E4: IgG2a, 7D4: IgM, PC61: IgG1) with respective Kd of 0.8, 0.2, and 0.85 nM and maximal binding capacities of 2 x 10(5), 4 x 10(5) sites per cell did not interfere with IL-2 binding and did not affect the IL-2-induced proliferation of the murine cell line. All three MoAbs were found to define three separate epitopic clusters independent of cluster I. Among them, only 2E4 induced a strong complement-mediated cytotoxicity. In vivo experiments showed that all MoAbs from cluster I were efficient in suppressing the DTH reaction and that the magnitude of their effect was consistent with their respective Kds. At a suboptimal dose of 1 microgram per day, the DTH inhibition indices were 40%, 43%, 23%, and 9% for 5A2, 125, 135, and AMT13, respectively. The 2E4 MoAb was found to be as efficient as cluster I MoAbs in suppressing DTH (53% inhibition at 1 microgram/day) while 7D4 and PC61 induced only a moderate inhibitory effect (37% inhibition for each MoAb given at 10 micrograms/day, compared with 70% inhibition for cluster I MoAbs). Taken together, our results indicate that blocking the IL-2/IL-2-R interaction without complement fixation is sufficient per se to attenuate the DTH reaction, and conversely that strong complement-mediated cytotoxicity in the absence of a functional effect in the IL-2/IL-2-R interaction is also effective in this system. Finally, no synergistic effect between MoAbs belonging to different clusters was evidenced in the DTH model.
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Papers by Y. Jacques