Interleukin-13 (IL-13) responsiveness was examined in lymph node B cells from patients with non-H... more Interleukin-13 (IL-13) responsiveness was examined in lymph node B cells from patients with non-Hodgkin's lymphoma (NHL) and patients with benign reactive immune disorders. Proliferation assays showed that NHL B cells from 8 of 21 patients responded to IL-13 in the absence of a co-activation signal. IL-13-unresponsive NHL B cells from 9 of the 13 remaining patients were induced to respond to IL-13 upon antibody-triggered CD40 activation, as did reactive B cells. Binding experiments with radiolabeled IL-13 revealed that the constitutive expression of IL-13 receptors (IL-13R) was associated with IL-13 responsiveness in the absence of CD40 activation. In IL-13-unresponsive cells, IL-13R expression was induced after CD40 activation. This effect was enhanced by IL-10, which was able to potentiate the IL-13 response of CD40-activated cells. Furthermore, IL-13 was found to increase the viability of cultured NHL cells, but not that of non-malignant cells. These results suggest that IL-1...
Oral presentations of conventional immunosuppressive therapy or being therapy-refractive, were in... more Oral presentations of conventional immunosuppressive therapy or being therapy-refractive, were included in this therapeutic trial. Patients received peptide three times a week over a twelve weeks period, while only low dose steroids were allowed as concomitant medication. The aim was to discontinue immunosuppressive therapy, to reduce steroids and simultaneously reduce relapses of ocular inflammation. T cell and antibody responses to the peptide were investigated. The Helsinki Declaration was strictly observed and the study design approved by the local ethical committee. lasting production of cytokine in the serum, compared to S.C. engraftment of the respective cells.. Compared to negative control groups, CIA was signfficantfy inhibited in groups transplanted with HF containing IL-4 or IL-13 transfected cells; this suppressive effect persisted until the end of the experiment (day 60). Conduslon: Encapsulation of antiinflammatory cytokines gene transfected cells is suitable and effectfve in CIA. Such encapsulation in HF may be useful in protecting the cells from rejection or removing them. Reeuk The first patients orally toletized wfth the HLA-peptide (two had stopped azathioprine immediately before onset of oral peptide) could discon-1 Treatment of newlv established transoenlc model of tin& their steroids because of reduced intraocular inflamm&on.'No side effects-chronic relapsing kthrltls wlth non-dipletlng antl of therapy was observed. In some patients, peptfde specific antibodies showed CD4 monoclonal antibody a shift from Thl to Th2 type antibodies. Condueion: Oral tolerance induction with a peptide, derived from the patient's own HfA-antigens and crossreactive wfth the autoantigen, seems to be a very potent therapeutic approach.
We have purified to near homogeneity the M-phasespecific protein kinase from starfish oocytes at ... more We have purified to near homogeneity the M-phasespecific protein kinase from starfish oocytes at first meiotic metaphase, using an improved procedure based on affinity chromatography on the immobilized yeast protein sucl. As already reported, this is identical to MPF, the cytoplasmic factor that controls entry of eukaryotic cells into M-phase. MPF is a complex formed by the stoichiometric association of a 34-kd polypeptide previously identified as cdc2 with a polypeptide that migrates with the same mobility as starfish cycin in SDS-PAGE (apparent mol. wt 47 kd). A cDNA clone encoding starfish cyclin B has been isolated and its sequence determined. It contains a single open reading frame encoding a predicted 43 729-dalton protein. Partial microsequencing of the 47-kd polypeptide component of MPF allowed its identification as the starfish cyclin. Since the apparent mol. wt of native starfish MPF was found to be <100 kd, it is a heterodimer comprising one molecule of cdc2 and one molecule of cyclin B.
We have examined in detail the activities of IL-13 on monokine production in vitro and compared i... more We have examined in detail the activities of IL-13 on monokine production in vitro and compared its effects with those of IL-10 and IFN-gamma. IL-13 and IL-10 show qualitatively and quantitatively similar activities on cytokine production by monocytes when administered simultaneously with LPS i.e. inhibition of IL-1, IL-6 and TNF-alpha, up-regulation of IL1-ra. However when either LPS and IFN-gamma or fixed S. aureus Cowan (SAC) are used to activate monocytes, IL-10 is a much more potent inhibitor of TNF-alpha production than is IL-13. IL-10 is also an extremely potent inhibitor of IL-12 (p70) production when given with either SAC or LPS, while IL-13 has little effect. Indeed, IL-13 actually increases SAC-induced IL-12 production. When IL-13 is administered prior to the LPS stimulation, its modulation of cytokine production is drastically different. Production of IL-12, MCP-1, TNF-alpha and to a lesser extent IL-6 induced by LPS is now "primed", whereas that of IL-1, IL-8,...
Abstract : Various aspects of solar flares such as dynamic phenomena, the relation to magnetic fi... more Abstract : Various aspects of solar flares such as dynamic phenomena, the relation to magnetic fields, electromagnetic radiations, particle emissions, and flare loops are discussed with attempts at classification in terms of observable effects. Discrepancies in defining the mechanisms that must exist stress the need for further observations. (Author)
The present study was designed to explore the interaction of interleukin-13 (IL-13) with vascular... more The present study was designed to explore the interaction of interleukin-13 (IL-13) with vascular endothelial cells (EC). In vitro exposure to IL-13 of human umbilical vein EC induced surface expression of vascular cell adhesion molecule-1 (VCAM-1). At optimal concentrations (10 to 50 ng/mL) and exposure times (24 hours), IL-13 was a twofold to threefold less effective inducer of VCAM-1 than IL-1, which was used as reference EC activator. When IL-13 was combined with IL-1, an almost additive induction of VCAM-1 was observed. Induction of VCAM-1 by IL-13 was selective in that E-selectin and intercellular adhesion molecule-1 (ICAM-1) were unaffected. IL-13 caused a modest reduction of IL-1 induction of E-selectin and ICAM-1. Surface expression of VCAM-1 on IL-13-treated cells was associated with mRNA induction (as assessed by Northern analysis and reverse transcriptase-polymerase chain reaction), with predominance of transcripts encoding the 7 Ig domain form of this molecule. In agree...
The peripheral benzodiazepine receptor (PBR) is an 18-kDa protein present in the outer mitochondr... more The peripheral benzodiazepine receptor (PBR) is an 18-kDa protein present in the outer mitochondrial membrane. The human PBR can be labeled with the benzodiazepine Ro5-4864 and with the isoquinoline carboxamide PK11195. The two ligands compete with each other in binding experiments, with previous results suggesting overlapping but not identical binding sites. To define the regions of the receptor interacting with PK11195 and Ro5-4864 and to address the question of the topology of the molecule in the membrane, we generated mutant human PBRs with amino- and carboxyl-terminal deletions and with point mutations in potentially accessible cytoplasmic regions. The mutant genes were expressed in yeast and analyzed in binding experiments using radiolabeled PK11195 and Ro5-4864. The results showed that, whereas deletions in the amino-terminal sequence had marked consequences for the binding affinity of both ligands, the final 13 amino acids at the carboxyl terminus could be deleted with no ef...
Experimental autoimmune encephalomyelitis (EAE) is initiated by myelin basic protein (MBP)-specif... more Experimental autoimmune encephalomyelitis (EAE) is initiated by myelin basic protein (MBP)-specific CD4+ T cells of the Th1 phenotype that subsequently trigger the invasion of monocytes/macrophages into the brain. In this study, we evaluated the potential of human recombinant (hr) IL-13 to exert a protective effect on the development of EAE in Lewis rats. hrIL-13 is found to be a potent in vitro modulator of various rat macrophage functions, including an inhibition of the production of the proinflammatory cytokines IL-1 beta and TNF, and a simultaneous enhancement of MHC class II and CD4 receptor expression. Furthermore, hrIL-13 displayed a slight, but highly reproducible, inhibitory effect on the in vitro proliferative responses of encephalitogenic MBP-specific T cells stimulated in the presence of thymic APCs. Upon in vivo application of hrIL-13-secreting vector cells into MBP-immunized animals, the cytokine was capable of markedly suppressing the development of EAE, as assessed b...
The IA4 mAb was identified among a series of antibodies raised in BALB/c mice after immunization ... more The IA4 mAb was identified among a series of antibodies raised in BALB/c mice after immunization against a HLA class I-deficient, lymphokine-activated killer (LAK)-susceptible EBV-B lymphocyte line. The IA4 antibody was selected because of its high expression, in the range of 10(5) to 25 x 10(5) sites/cell, on several B lymphocyte lines (EBV-transformed or Burkitt) and monocytic lines such as HL60 and U937, and because its expression was correlated with both target susceptibility to LAK lysis and reduced expression of HLA class I surface Ag on two pairs of EBV-B-transformed cell lines (721/721.134 and MM/10F2). Despite the strategy followed to raise the mAb and the correlation mentioned above, no direct role of the IA4 molecules in LAK susceptibility has been established, since the IA4 molecule is poorly expressed on the sensitive targets Daudi and K562; moreover, the IA4 antibody did not affect reproducibly the in vitro killing of positive target cells by LAK effectors. The IA4 ant...
We have compared the production of the related cytokines IL-13 and IL-4 by T lymphocytes, and the... more We have compared the production of the related cytokines IL-13 and IL-4 by T lymphocytes, and the effects of the two cytokines on these cells. IL-13 and IL-4 production differ in a number of respects. IL-13 is produced at higher levels than IL-4 by activated T lymphocytes, and its accumulation in the culture medium can be more prolonged, corresponding partly to differential mRNA accumulation and partly to a preferential depletion of IL-4 from the culture medium. Certain inducing combinations such as PMA and anti-CD28, stimulate high levels of IL-13 and IL-13 mRNA, but little or no IL-4 or IL-4 mRNA. The ratio of IL-13 to IL-4, both at protein and mRNA levels, is higher in CD8+ lymphocyte than in CD4+ lymphocyte populations. Although after in vitro polarization of peripheral blood lymphocytes leading to type 1 and type 2 populations, IL-13 is made principally by cells of a type 2 phenotype, as is IL-4; it can also be produced by type 1 CD4+ and CD8+ T lymphocyte clones making large a...
This introductory paper reviews new ideas concerning regulatory T cells, in the fields of hyperre... more This introductory paper reviews new ideas concerning regulatory T cells, in the fields of hyperreactivity, cytokine balance, and desequestration of self-antigens. It also summarises an older and more troubled theme in network research, the influence on these cells of IgV regions.
The beta 3 adrenergic receptor stimulates lipolysis and colonic relaxation in the rat, and, sugge... more The beta 3 adrenergic receptor stimulates lipolysis and colonic relaxation in the rat, and, suggestively, in man. Several human forms generated by different mRNA splicings can occur: the A form of 396 amino acids and the B and C forms extended by 12 and 6 amino acids respectively, in the C-terminus region. In order to characterize these different forms as expressed in CHO cells, we studied adenylyl cyclase stimulation by the beta 3 agonists, SR58611A and BRL37344 and its inhibition by the beta 3 antagonist SR59230. This antagonist totally inhibited SR58611-adenylyl cyclase stimulation with the following hierarchy of potency: C form > B > A. In rat, a unique form is expressed which is close to the human B form. This form was the less sensitive to beta 1 and beta 2 antagonists. These findings constitute a molecular pharmacological basis for the design of beta 3 agonists of therapeutic value.
In HIV-1-infected monocytes and monocytoid cell lines, viral expression can be observed as high-l... more In HIV-1-infected monocytes and monocytoid cell lines, viral expression can be observed as high-level production, restricted (chronic low-level) expression, and latency (no viral expression). Interleukin-13 (IL-13) and IL-4, which have remarkedly similar deactivating effects on inflammatory monocyte functions, were studied for their regulation of HIV expression in monocytes. Pretreatment of peripheral monocytes for 48-72 h with IL-13 markedly decreased acute HIV infection, whereas IL-4 increased it. Similar effects were seen when the U1 and R-THP-1 monocytoid cell lines with restricted HIV expression were treated with these cytokines. However, when these continuously producing cell lines were chronically treated with cytokines, IL-13 increased HIV production. Neither IL-4 nor IL-13 stimulated HIV expression in latently infected cells. In chronically infected cells, several cytokines reduced viral mRNA. Both IL-4 and IL-13 increased monocyte aggregate formation, but only IL-4 ultimat...
Myoblasts cultivated in vitro will undergo terminal differentiation to form muscle fibres. Terato... more Myoblasts cultivated in vitro will undergo terminal differentiation to form muscle fibres. Teratoma derived mouse cell lines, a pluripotent primitive line, and a muscle cell line, provide a possibility for comparing RNA populations in an early precursor cell with those in committed myoblasts and differentiated myotubes. Molecular hybridization analyses led to the conclusion that new RNA sequences appear in the cytoplasm during muscle differentiation. Such muscle specific sequences are not detectable in the nuclear RNA of myoblasts or primitive cells. Studies of protein synthesis during terminal myogenesis indicate co-ordinate expression of the muscle contractile proteins. These represent distinct isozymes, distinguishable from the contractile proteins of other cell types. In the case of myosin light chains isozymic transitions between different muscle forms have been identified during early development.
role of the y,-chain in human B-cell responses to IL-2, IL-4, IL-13, and IL-15. Our experiments s... more role of the y,-chain in human B-cell responses to IL-2, IL-4, IL-13, and IL-15. Our experiments show that B cells from two X-SCID patients with characterized yc-chain gene mutations do not respond to IL-2 or IL-15, but respond as well or better than normal B cells to both IL-4 and IL-13 in assays for Bcell activation, proliferation, and IgE secretion. This finding raises important questions about the function of the yc-chain in receptors for IL-4 and IL-13, and the nature of the immune defect in X-SCID.
Interleukin-13 (IL-13) responsiveness was examined in lymph node B cells from patients with non-H... more Interleukin-13 (IL-13) responsiveness was examined in lymph node B cells from patients with non-Hodgkin's lymphoma (NHL) and patients with benign reactive immune disorders. Proliferation assays showed that NHL B cells from 8 of 21 patients responded to IL-13 in the absence of a co-activation signal. IL-13-unresponsive NHL B cells from 9 of the 13 remaining patients were induced to respond to IL-13 upon antibody-triggered CD40 activation, as did reactive B cells. Binding experiments with radiolabeled IL-13 revealed that the constitutive expression of IL-13 receptors (IL-13R) was associated with IL-13 responsiveness in the absence of CD40 activation. In IL-13-unresponsive cells, IL-13R expression was induced after CD40 activation. This effect was enhanced by IL-10, which was able to potentiate the IL-13 response of CD40-activated cells. Furthermore, IL-13 was found to increase the viability of cultured NHL cells, but not that of non-malignant cells. These results suggest that IL-1...
Oral presentations of conventional immunosuppressive therapy or being therapy-refractive, were in... more Oral presentations of conventional immunosuppressive therapy or being therapy-refractive, were included in this therapeutic trial. Patients received peptide three times a week over a twelve weeks period, while only low dose steroids were allowed as concomitant medication. The aim was to discontinue immunosuppressive therapy, to reduce steroids and simultaneously reduce relapses of ocular inflammation. T cell and antibody responses to the peptide were investigated. The Helsinki Declaration was strictly observed and the study design approved by the local ethical committee. lasting production of cytokine in the serum, compared to S.C. engraftment of the respective cells.. Compared to negative control groups, CIA was signfficantfy inhibited in groups transplanted with HF containing IL-4 or IL-13 transfected cells; this suppressive effect persisted until the end of the experiment (day 60). Conduslon: Encapsulation of antiinflammatory cytokines gene transfected cells is suitable and effectfve in CIA. Such encapsulation in HF may be useful in protecting the cells from rejection or removing them. Reeuk The first patients orally toletized wfth the HLA-peptide (two had stopped azathioprine immediately before onset of oral peptide) could discon-1 Treatment of newlv established transoenlc model of tin& their steroids because of reduced intraocular inflamm&on.'No side effects-chronic relapsing kthrltls wlth non-dipletlng antl of therapy was observed. In some patients, peptfde specific antibodies showed CD4 monoclonal antibody a shift from Thl to Th2 type antibodies. Condueion: Oral tolerance induction with a peptide, derived from the patient's own HfA-antigens and crossreactive wfth the autoantigen, seems to be a very potent therapeutic approach.
We have purified to near homogeneity the M-phasespecific protein kinase from starfish oocytes at ... more We have purified to near homogeneity the M-phasespecific protein kinase from starfish oocytes at first meiotic metaphase, using an improved procedure based on affinity chromatography on the immobilized yeast protein sucl. As already reported, this is identical to MPF, the cytoplasmic factor that controls entry of eukaryotic cells into M-phase. MPF is a complex formed by the stoichiometric association of a 34-kd polypeptide previously identified as cdc2 with a polypeptide that migrates with the same mobility as starfish cycin in SDS-PAGE (apparent mol. wt 47 kd). A cDNA clone encoding starfish cyclin B has been isolated and its sequence determined. It contains a single open reading frame encoding a predicted 43 729-dalton protein. Partial microsequencing of the 47-kd polypeptide component of MPF allowed its identification as the starfish cyclin. Since the apparent mol. wt of native starfish MPF was found to be <100 kd, it is a heterodimer comprising one molecule of cdc2 and one molecule of cyclin B.
We have examined in detail the activities of IL-13 on monokine production in vitro and compared i... more We have examined in detail the activities of IL-13 on monokine production in vitro and compared its effects with those of IL-10 and IFN-gamma. IL-13 and IL-10 show qualitatively and quantitatively similar activities on cytokine production by monocytes when administered simultaneously with LPS i.e. inhibition of IL-1, IL-6 and TNF-alpha, up-regulation of IL1-ra. However when either LPS and IFN-gamma or fixed S. aureus Cowan (SAC) are used to activate monocytes, IL-10 is a much more potent inhibitor of TNF-alpha production than is IL-13. IL-10 is also an extremely potent inhibitor of IL-12 (p70) production when given with either SAC or LPS, while IL-13 has little effect. Indeed, IL-13 actually increases SAC-induced IL-12 production. When IL-13 is administered prior to the LPS stimulation, its modulation of cytokine production is drastically different. Production of IL-12, MCP-1, TNF-alpha and to a lesser extent IL-6 induced by LPS is now "primed", whereas that of IL-1, IL-8,...
Abstract : Various aspects of solar flares such as dynamic phenomena, the relation to magnetic fi... more Abstract : Various aspects of solar flares such as dynamic phenomena, the relation to magnetic fields, electromagnetic radiations, particle emissions, and flare loops are discussed with attempts at classification in terms of observable effects. Discrepancies in defining the mechanisms that must exist stress the need for further observations. (Author)
The present study was designed to explore the interaction of interleukin-13 (IL-13) with vascular... more The present study was designed to explore the interaction of interleukin-13 (IL-13) with vascular endothelial cells (EC). In vitro exposure to IL-13 of human umbilical vein EC induced surface expression of vascular cell adhesion molecule-1 (VCAM-1). At optimal concentrations (10 to 50 ng/mL) and exposure times (24 hours), IL-13 was a twofold to threefold less effective inducer of VCAM-1 than IL-1, which was used as reference EC activator. When IL-13 was combined with IL-1, an almost additive induction of VCAM-1 was observed. Induction of VCAM-1 by IL-13 was selective in that E-selectin and intercellular adhesion molecule-1 (ICAM-1) were unaffected. IL-13 caused a modest reduction of IL-1 induction of E-selectin and ICAM-1. Surface expression of VCAM-1 on IL-13-treated cells was associated with mRNA induction (as assessed by Northern analysis and reverse transcriptase-polymerase chain reaction), with predominance of transcripts encoding the 7 Ig domain form of this molecule. In agree...
The peripheral benzodiazepine receptor (PBR) is an 18-kDa protein present in the outer mitochondr... more The peripheral benzodiazepine receptor (PBR) is an 18-kDa protein present in the outer mitochondrial membrane. The human PBR can be labeled with the benzodiazepine Ro5-4864 and with the isoquinoline carboxamide PK11195. The two ligands compete with each other in binding experiments, with previous results suggesting overlapping but not identical binding sites. To define the regions of the receptor interacting with PK11195 and Ro5-4864 and to address the question of the topology of the molecule in the membrane, we generated mutant human PBRs with amino- and carboxyl-terminal deletions and with point mutations in potentially accessible cytoplasmic regions. The mutant genes were expressed in yeast and analyzed in binding experiments using radiolabeled PK11195 and Ro5-4864. The results showed that, whereas deletions in the amino-terminal sequence had marked consequences for the binding affinity of both ligands, the final 13 amino acids at the carboxyl terminus could be deleted with no ef...
Experimental autoimmune encephalomyelitis (EAE) is initiated by myelin basic protein (MBP)-specif... more Experimental autoimmune encephalomyelitis (EAE) is initiated by myelin basic protein (MBP)-specific CD4+ T cells of the Th1 phenotype that subsequently trigger the invasion of monocytes/macrophages into the brain. In this study, we evaluated the potential of human recombinant (hr) IL-13 to exert a protective effect on the development of EAE in Lewis rats. hrIL-13 is found to be a potent in vitro modulator of various rat macrophage functions, including an inhibition of the production of the proinflammatory cytokines IL-1 beta and TNF, and a simultaneous enhancement of MHC class II and CD4 receptor expression. Furthermore, hrIL-13 displayed a slight, but highly reproducible, inhibitory effect on the in vitro proliferative responses of encephalitogenic MBP-specific T cells stimulated in the presence of thymic APCs. Upon in vivo application of hrIL-13-secreting vector cells into MBP-immunized animals, the cytokine was capable of markedly suppressing the development of EAE, as assessed b...
The IA4 mAb was identified among a series of antibodies raised in BALB/c mice after immunization ... more The IA4 mAb was identified among a series of antibodies raised in BALB/c mice after immunization against a HLA class I-deficient, lymphokine-activated killer (LAK)-susceptible EBV-B lymphocyte line. The IA4 antibody was selected because of its high expression, in the range of 10(5) to 25 x 10(5) sites/cell, on several B lymphocyte lines (EBV-transformed or Burkitt) and monocytic lines such as HL60 and U937, and because its expression was correlated with both target susceptibility to LAK lysis and reduced expression of HLA class I surface Ag on two pairs of EBV-B-transformed cell lines (721/721.134 and MM/10F2). Despite the strategy followed to raise the mAb and the correlation mentioned above, no direct role of the IA4 molecules in LAK susceptibility has been established, since the IA4 molecule is poorly expressed on the sensitive targets Daudi and K562; moreover, the IA4 antibody did not affect reproducibly the in vitro killing of positive target cells by LAK effectors. The IA4 ant...
We have compared the production of the related cytokines IL-13 and IL-4 by T lymphocytes, and the... more We have compared the production of the related cytokines IL-13 and IL-4 by T lymphocytes, and the effects of the two cytokines on these cells. IL-13 and IL-4 production differ in a number of respects. IL-13 is produced at higher levels than IL-4 by activated T lymphocytes, and its accumulation in the culture medium can be more prolonged, corresponding partly to differential mRNA accumulation and partly to a preferential depletion of IL-4 from the culture medium. Certain inducing combinations such as PMA and anti-CD28, stimulate high levels of IL-13 and IL-13 mRNA, but little or no IL-4 or IL-4 mRNA. The ratio of IL-13 to IL-4, both at protein and mRNA levels, is higher in CD8+ lymphocyte than in CD4+ lymphocyte populations. Although after in vitro polarization of peripheral blood lymphocytes leading to type 1 and type 2 populations, IL-13 is made principally by cells of a type 2 phenotype, as is IL-4; it can also be produced by type 1 CD4+ and CD8+ T lymphocyte clones making large a...
This introductory paper reviews new ideas concerning regulatory T cells, in the fields of hyperre... more This introductory paper reviews new ideas concerning regulatory T cells, in the fields of hyperreactivity, cytokine balance, and desequestration of self-antigens. It also summarises an older and more troubled theme in network research, the influence on these cells of IgV regions.
The beta 3 adrenergic receptor stimulates lipolysis and colonic relaxation in the rat, and, sugge... more The beta 3 adrenergic receptor stimulates lipolysis and colonic relaxation in the rat, and, suggestively, in man. Several human forms generated by different mRNA splicings can occur: the A form of 396 amino acids and the B and C forms extended by 12 and 6 amino acids respectively, in the C-terminus region. In order to characterize these different forms as expressed in CHO cells, we studied adenylyl cyclase stimulation by the beta 3 agonists, SR58611A and BRL37344 and its inhibition by the beta 3 antagonist SR59230. This antagonist totally inhibited SR58611-adenylyl cyclase stimulation with the following hierarchy of potency: C form > B > A. In rat, a unique form is expressed which is close to the human B form. This form was the less sensitive to beta 1 and beta 2 antagonists. These findings constitute a molecular pharmacological basis for the design of beta 3 agonists of therapeutic value.
In HIV-1-infected monocytes and monocytoid cell lines, viral expression can be observed as high-l... more In HIV-1-infected monocytes and monocytoid cell lines, viral expression can be observed as high-level production, restricted (chronic low-level) expression, and latency (no viral expression). Interleukin-13 (IL-13) and IL-4, which have remarkedly similar deactivating effects on inflammatory monocyte functions, were studied for their regulation of HIV expression in monocytes. Pretreatment of peripheral monocytes for 48-72 h with IL-13 markedly decreased acute HIV infection, whereas IL-4 increased it. Similar effects were seen when the U1 and R-THP-1 monocytoid cell lines with restricted HIV expression were treated with these cytokines. However, when these continuously producing cell lines were chronically treated with cytokines, IL-13 increased HIV production. Neither IL-4 nor IL-13 stimulated HIV expression in latently infected cells. In chronically infected cells, several cytokines reduced viral mRNA. Both IL-4 and IL-13 increased monocyte aggregate formation, but only IL-4 ultimat...
Myoblasts cultivated in vitro will undergo terminal differentiation to form muscle fibres. Terato... more Myoblasts cultivated in vitro will undergo terminal differentiation to form muscle fibres. Teratoma derived mouse cell lines, a pluripotent primitive line, and a muscle cell line, provide a possibility for comparing RNA populations in an early precursor cell with those in committed myoblasts and differentiated myotubes. Molecular hybridization analyses led to the conclusion that new RNA sequences appear in the cytoplasm during muscle differentiation. Such muscle specific sequences are not detectable in the nuclear RNA of myoblasts or primitive cells. Studies of protein synthesis during terminal myogenesis indicate co-ordinate expression of the muscle contractile proteins. These represent distinct isozymes, distinguishable from the contractile proteins of other cell types. In the case of myosin light chains isozymic transitions between different muscle forms have been identified during early development.
role of the y,-chain in human B-cell responses to IL-2, IL-4, IL-13, and IL-15. Our experiments s... more role of the y,-chain in human B-cell responses to IL-2, IL-4, IL-13, and IL-15. Our experiments show that B cells from two X-SCID patients with characterized yc-chain gene mutations do not respond to IL-2 or IL-15, but respond as well or better than normal B cells to both IL-4 and IL-13 in assays for Bcell activation, proliferation, and IgE secretion. This finding raises important questions about the function of the yc-chain in receptors for IL-4 and IL-13, and the nature of the immune defect in X-SCID.
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Papers by Daniel Caput