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J Hiernaux

Publications and source records attributed to J Hiernaux.

At least 19 recordsLinked to original sources
PubMed1992

On the kinetics and optimal specificity of cytotoxic reactions mediated by T-lymphocyte clones.

Using the chromium release assay and the single cell assay in agarose, we study the cytotoxic reaction of the MHC-restricted T lymphocyte clones P89:15 and P1:3, which recognize distinct but specific tumour antigens on the surface of syngeneic P815 mastocytoma cells. We propose a mathematical model which describes these experiments, accounts for the strongly non-Michaelian behaviour of the reaction and permits us to estimate the kinetic parameters characterizing effector-target conjugation and lethal hit delivery. The results show that the binding and lytic activity of effector cells is modulated by the number of targets bound to them. The binding of a second target by an effector having already a target bound is facilitated; on the other hand, an effector having bound two targets delivers a lethal hit more slowly than one with a single target bound. We investigate the role of these kinetic properties in the competition between the process of tumour progression due to cancer cell replication and the process of tumour regression due to T lymphocyte cytotoxic activity. For both clones, we estimate the effector-target ratio beyond which rejection prevails. This ratio is nine times larger for P1:3 than for P89:15. Furthermore, our analysis suggests that there exists an optimal specificity minimizing this ratio. Deviations from this optimum, be it in the sense of an increase or decrease of specificity, tends to stabilize the tumoural state: a situation which in the broader context of the immune response evolution and regulation can be viewed as an immune response dilemma.

Animals↗
PubMed1991

Refractory period phenomenon in the induction of tissue factor expression on endothelial cells.

Tissue factor (TF) is the first factor of the extrinsic pathway of coagulation. Normally, TF is not expressed on the surface of endothelial cells. However, expression of TF can be induced in these cells in response to stimulation by diverse inflammatory mediators such as interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), lipopolysaccharide (LPS), and phorbol 12-myristate 13-acetate (PMA). We have studied the effect of these mediators on the kinetics of the induction of TF-related procoagulant activity (PCA) on human umbilical vein endothelial cells (HUVECs). PCA is transiently induced on HUVECs, attaining a peak some 4 to 8 hours after addition of inflammatory agents, with maximal accumulation of TF messenger RNA (mRNA) occurring 3 to 5 hours earlier. Because the expression of PCA by treated HUVECs returns to basal levels by 20 to 30 hours, we examined the response of these cells to a second inflammatory stimulus. Continuous incubation of cells with a single inflammatory agent for 24 to 48 hours induces a hyporesponsive state with respect to the reinduction of TF expression by the same agent (14% of the initial stimulation for IL-1 beta, 39% for TNF-alpha 30% for LPS, and 7% for PMA). Such a diminution in PCA was also observed in the levels of TF mRNA. By contrast, pretreatment of HUVECs with one agent did not dramatically affect the reinduction of TF by any of the three other factors. We subsequently focused our attention on the induction of the autologous refractory period by IL-1 beta. De novo protein synthesis was not required during the preincubation of ECs for hyporesponsiveness to be observed. The establishment of the refractory state did not depend on the downmodulation of IL-1 beta receptor affinity or expression. Moreover, pretreatment of HUVECs with IL-1 beta increased prostacyclin (PGI2) production in response to a second stimulation by IL-1 beta, although such cells were unable to reexpress TF under the same conditions. This result suggests that distinct secondary messenger pathways are involved in TF induction and PGI2 synthesis by IL-1 beta in HUVECs.

Endothelium, Vascular↗
PubMed1988

Kinetics of cellular cytotoxicity mediated by cloned cytotoxic T lymphocytes.

Kinetic methods can provide significant information concerning the mechanism of cellular cytotoxicity reactions. Previous kinetic studies of cytotoxic T lymphocytes (Tc) have been hampered by the heterogeneity of the effector cell population tested. We therefore examined the kinetics of lysis mediated by cloned, IL 2 and antigen-dependent murine Tc cells with strong cytotoxic activity that is restricted to distinct tumor-associated antigens on P815 mastocytoma target cells. Initial velocity measurements for cytotoxicity mediated by these clones fit a simple Michaelian kinetic model. Specific activity values obtained from these initial rate measurements are compared to those obtained for polyclonal Tc preparations, NK cells, and activated killer cells. Whereas the initial rate of lytic programming mediated by these cloned cells was very rapid, the rate of cytolysis mediated by the cloned cells decreased significantly within one hour. Since this decrease was observed over a wide range of E:T ratios, it is unlikely to result from product inhibition or a significant decrease in the concentration of unlysed target cells, but may be due to a decrease in the rate of programming and/or effector cell recycling. These results indicate that a simple Michaelian kinetic model is not adequate for tumor cell cytolysis by Tc cells in vitro.

Animals↗
PubMed1985

Idiotypic analysis of polyclonal and monoclonal anti-p-azophenylarsonate antibodies of BALB/c mice expressing the major cross-reactive idiotype of the A/J strain.

The idiotypic cascade allows the induction of silent idiotypes, and as such, the immune system can be reprogrammed towards predetermined goals. To understand the genetic origin of silent idiotypes, we have used a system in which detailed structural and genetic information is available. The major cross-reactive idiotype (CRIA) of A/J mice (positive strain) immunized with arsonate coupled to a carrier can be regularly induced in BALB/c mice (negative strain) by anti-idiotypic treatment with or without subsequent antigen immunization. By using a panel of monoclonal anti-idiotypic antibodies, we have found that the germline-encoded CRIA displays a mosaic of at least five idiotopes. Polyclonal and monoclonal anti-arsonate antibodies prepared from idiotypically manipulated BALB/c mice have been studied. Four germline idiotopes are shared between the CRIA of the A/J strain and the CRIA-like idiotype induced in BALB/c mice. Furthermore, CRIA-like antibodies can appear "spontaneously" in some BALB/c mice immunized with antigen only. The data suggest that anti-idiotypic treatment in BALB/c mice selects a preexisting subset of antibodies. From the serological analysis, it is predicted that CRIA molecules from A/J and CRIA-like molecules from BALB/c employ different VH subgroups but share some components of the hypervariable regions. These predictions are tested in a forthcoming paper that describes the amino acid sequences of BALB/c monoclonal antibodies displaying the major cross-reactive idiotype of the A/J strain.

Amino Acid Sequence↗
PubMed1984

Idiotypic analysis of potential and available repertoires in the arsonate system.

We have shown that, by suitable idiotypic manipulation, BALB/c mice can express the major cross-reactive idiotype (CRI) of A/J mice in response to azophenylarsonate (Ars). In order to know if the CRIA idiotype is present in the potential repertoire of BALB/c before any intentional selection, we used polyclonal activation in vitro and limiting dilution analysis. The readout was done with two monoclonal anti-CRIA antibodies that recognize distinct idiotopes on a CRIA+ A/J germline-encoded monoclonal antibody. We studied the frequency of CRIA+ lipopolysaccharide (LPS)-reactive cells in the spleens of nonimmune and immune A/J mice and in the spleens of naive and manipulated (i.e., producing CRIA+ antibodies) BALB/c mice. A/J and BALB/c naive individuals presented very high frequencies of Ars-specific B cells while the frequency of CRIA+ B cells was only a minor subset (0.5%) of the total Ars-specific subset in the two strains. When A/J mice were immunized with Ars-keyhole limpet hemocyanin, a clear preferential expansion of the CRIA+ minor subset of A/J mice was observed (100x). No such enhancement was observed in BALB/c mice similarly treated. Manipulated BALB/c mice presented a higher frequency of CRIA+ anti-Ars B cells than naive or antigen-immunized BALB/c individuals.

Animals↗
PubMed1983

Idiotype-antiidiotype regulation. V. The requirement for immunization with antigen or monoclonal antiidiotypic antibodies for the activation of beta 2 leads to 6 and beta 2 leads to 1 polyfructosan-reactive clones in BALB/c mice treated at birth with minute amounts of anti-A48 idiotype antibodies.

The anti-beta 2 leads to 6 fructosan antibodies sharing the idiotypes (Id) of ABPC48 (A48) monoclonal protein represent a silent fraction of the anti-beta 2 leads to 6 fructosan repertoire, since these antibodies cannot be detected during a conventional immune response elicited by bacterial levan (BL). However, the administration at birth of minute amounts of anti-A48 Id antibodies causes a long-lasting activation of A48 Id+-bearing clones. This activation is related to direct interaction of anti-A48 Id antibodies with precursors bearing the A48 Id+ immunoglobulin receptor, since an A48 Id+ response can be transferred with highly purified B cells in lethally irradiated mice. The maturation of these precursors into A48 Id+ anti-beta 2 leads to 6 fructosan antibody-secreting cells requires challenge by the antigen. Isoelectric focusing (IEF) data showed that in 1-mo-old mice an UPC10 (U10)-like spectrotype was observed, whereas in 3-mo-old mice, a new spectrotype binding BL rather than inulin (In) was identified. This spectrotype was observed only in CXBJ mice, the single strain in which an A48 Id+ response was observed. The antigenic challenge can be replaced by a monoclonal anti-A48 Id antibody (i.e., 17-38). Interestingly, in 1-mo-old BALB/c mice treated with anti-A48 Id antibodies, the challenge with 17-38 monoclonal antibody led to the activation of A48 Id- anti-beta 2 leads to 6 fructosan-reactive clones with BALB/c type IEF spectrotypes, whereas in 3-mo-old BALB/c mice treated with anti-A48 Id antibodies, the challenge with 17-38 monoclonal antibody led to the activation of W3082 IdX+ anti-beta 2 leads to 6 and beta 2 leads to 1 fructosan-reactive clones. In these animals, inhibition of A48 Id+ anti-beta 2 leads to 6 fructosan clones was observed. This antibody probably represents a homobody carrying the internal image of the antigen, which through its paratope suppresses the A48 Id+ response and through its Id activates an A48 Id- anti-beta 2 leads to 6 fructosan response in 1-mo-old mice and in 3-mo-old mice leads to an anti-beta 2 leads to 6 and beta 2 leads to 1 fructosan response dominated by the W3082 IdX.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1983

Thymus-independent immunogenicity in vitro of the divalent antigen DNP-polyethylene oxide.

Chemically simple and physically well-defined dinitrophenyl derivatives of polyethylene oxide (DNP-PEO) can be prepared in a wide range of forms and sizes. These materials were used to investigate the molecular basis of immunogenicity and the binding of the antigens to membrane-bound receptors. Both di- and multivalent DNP-PEO activate normal murine B lymphocytes to yield primary anti-DNP antibody response in vitro. The immunogenicity is dependent on the carrier chain length but independent of T cells. Responses comparable to those induced by DNP-conjugated polymerized flagellin are induced by divalent linear materials of medium molecular weights of about 60,000. A highly multivalent material is moderately immunogenic, but at much lower antigen doses than divalent materials. The carrier PEO does not affect B-cell responses to DNP-PEO or T-cell response to succinyl concanavalin A. Moreover, it shows no polyclonal mitogenicity at concentrations as high as 1 mg/ml. Studies of antigen binding to cell surface DNP receptors show that the strongly immunogenic materials of medium molecular weights have an appreciable tendency to bind bivalently and thus potentially to crosslink receptors. The binding of smaller, less immunogenic antigen appears predominantly monovalent.

Animals↗
PubMed1983

Idiotypic manipulation in mice: BALB/c mice can express the crossreactive idiotype of A/J mice.

The response of A/J mice to arsonate-coupled keyhole limpet hemocyanin is characterized by a crossreactive idiotype (CRIA). CRIA+ antibodies are restricted to the Igh-Ic haplotype and are never expressed in BALB/c mice after immunization with antigen. Studies at the DNA level suggest that the gene encoding the CRIA heavy chain in A/J mice is probably absent in the genome of BALB/c mice. Despite this, using the immunization cascade tool, we have been able to induce the expression of CRIA+ antibodies in BALB/c mice. These studies led to an apparent paradox, whose understanding will provide new insights into the regulatory mechanisms of the immune system. We suggest that clones secreting CRIA-like Igs in BALB/c mice are "somatic variants" that could arise from gene conversion events.

Animals↗
PubMed1982

Shared idiotypes among monoclonal antibodies specific for different immunodominant sugars of lipopolysaccharide of different Gram-negative bacteria.

Shared idiotypes (Ids) were identified on monoclonal antibodies specific for different immunodominant sugars in the lipopolysaccharide (LPS) of Gram-negative bacteria. The first group of monoclonal antibodies is specific for Escherichia coli 0113 LPS, whereas the second group is specific for Salmonella tranaroa LPS. The shared idiotopes borne by these two groups of monoclonal antibodies were identified with monoclonal anti-Id antibodies specific for E. coli LPS-binding monoclonal antibodies and with syngeneic anti-384Id antibodies specific for MOPC 384 and MOPC 870 myeloma proteins. Our data suggest that shared idiotopes are common for antibodies for an antigenic family.

Antibodies, Monoclonal↗
PubMed1982

RIIIS/J mice lack a gene influencing the capacity to make an antibody response to helper T cell-independent antigens.

RIIIS/J mice lack an autosomal dominant gene(s) that has a decisive influence in determining the capacity to make an IgM antibody response to several representative helper T cell-independent antigens; these mice appear to possess functionally active helper T cells because of their ability to make a reasonably good antibody response to SRBC, a helper T cell-dependent antigen. The genetic defect involved cannot be attributed to the absence of B cells capable of giving a mitogenic response to bacterial LPS.

Animals↗
PubMed1981

Neonatal treatment with low doses of anti-idiotypic antibody leads to the expression of a silent clone.

BALB/c mice immunized with bacterial levan (BL) produce an immune response that fails to generate antibody expressing the idiotype (Id) of the beta (2 leads to 6) fructosan-binding myeloma protein ABPC 48 (A48). Pretreatment of newborn BALB/c mice (at 1 d of age) with 0.01-10 microgram of affinity purified BALB/c anti-A48 Id antibody followed by immunization with BL 1-2 mo later produces an anti-BL response that expresses the A48 Id. This shows that A48 Id+ anti-BL clones belong to a normally silent fraction of the anti-BL repertoire. The activation of A48 Id+ anti-BL clones anti-A48 Id antibody is specific because the pretreatment of newborn mice with anti-MOPC 384 Id antibody, followed by immunization with BL, does not lead to its activation. Moreover, pretreatment of mice with anti-A48 Id antibody does not alter the MOPC 460 Id+ component of the anti-TNP response. It is also important to note that the activation of the A48 Id+ clone in pretreated mice requires subsequent immunization with BL.

Animals↗
PubMed1981

Antiidiotypic networks.

Jerne envisions the immune system as a web of V domains that constitutes an idiotypic network. He thinks that regulatory processes governed by idiotypic interactions can explain the generation of the various immune states. We discuss a few models that furnish information about the possible configuration of this immune network: closed or open ended. It appears that closed configurations only can generate stable immune states. Moreover, we cite some experimental data in favor of the network hypothesis. We show how they can lead to propose the structure of functional regulatory circuits whose cellular and molecular interactions are mediated by idiotypic recognition processes.

Antibodies, Anti-Idiotypic↗
PubMed1980

Transition from polar to duplicate patterns.

The existence of symmetric nonuniform solutions in nonlinear reaction-diffusion systems is examined. In the first part of the paper, we establish systematically the bifurcation diagram of small amplitude solutions in the vicinity of the two first bifurcation points. It is shown that: i)The system can adopt a stable symmetric solution (basic wave number 2) if the value of the bifurcation parameter is changed or if the initial polar structure (basic wave number 1) is sufficiently perturbed. ii) This behavior is independent of the particular reaction-diffusion model proposed and of the number of intermediate components (greater than or equal to 2) involved. In the second part of the paper, analogies are established between the possibilities offered by the bifurcation diagrams, involving only the two first primary branches, the observation that in the early development of different organisms, appropraite experimental manipulations may switch the normal (polar) developmental pattern to a duplicate structure.

Animals↗
PubMed1979

Anthropometric differences between sicklers and nonsicklers in Zairian adults.

From a sample of 1,079 male adult Zairians living in regions where falciparum malaria is endemic 212 sicklers and 867 nonsicklers were compared for eight anthropometric variables. The two groups did not differ significantly in their variances. The sicklers had a higher mean for seven variables, but significantly so for head breadth only. These results are discussed in terms of the balance of the possible effects of the AS genotype on growth and of the possible selective effects of death from malaria in infancy.

Adult↗