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M Slaoui

Publications and source records attributed to M Slaoui.

50 records · Page 3Linked to original sources
PubMed1986

Idiotypic games within the immune network.

In this paper, we have considered the problem of selection of available repertoires. With Ab2 as immunogens, we have used the idiotypic cascade to explore potential repertoires. Our results suggest that potential idiotypic repertoires are more or less the same within a species or between different species. A given idiotype "à la Oudin" can become a recurrent one within the same outbred species or within different species. Similarly, an intrastrain crossreactive idiotype can be induced in other strains, even though there is a genetic disparity between these strains. The structural basis of this phenomenon has been explored. We next examined results showing the loss and gain of recurrent idiotypes without any intentional idiotypic manipulation. A recurrent idiotype can be lost in a syngeneic transfer and a private one can become recurrent by changing the genetic background. The change of available idiotypic repertoires at the B cell level has profound influences on the idiotypic repertoires of suppressor T cells. All these results imply that idiotypic games are played by the immune system itself, a strong suggestion that the immune system is a functional idiotypic network.

Animals↗
PubMed1985

Genetic and biological characterization of a T suppressor cell induced by anti-idiotypic antibody.

The cellular and molecular characteristics of anti-idiotype-induced suppression have been investigated. We have shown that i.v. immunization of A/J or C.AL-20 mice with rabbit antibodies against the major cross-reactive idiotype on A/J anti-ABA antibodies induces splenic suppressor T cells (Ts) able to suppress T cell-mediated cytolytic and delayed-type hypersensitivity responses to ABA. In these studies, we compare the T suppressor activity manifested by anti-Id-induced suppressor cells with that described previously after conventional antigen priming. Results indicate that i.v. injection of anti-idiotypic antibodies primes for efferent level Ts; in contrast, i.v. administration of ABA-coupled cells induces afferent level suppressor cells. Soluble cell lysates, containing suppressor factor(s) derived from these anti-idiotype-induced Ts, can also mediate suppression of T cell immune responses in an efferent manner. Factor-mediated suppression is MHC-unrestricted and is also observed in mice pretreated with cyclophosphamide, suggesting that this activity is analogous to third-order suppression. Furthermore, this factor suppresses the T cell-mediated DTH and CTL responses in an antigen-nonspecific but Igh-restricted manner. These latter results suggest that the cellular elements conferring antigen specificity and Igh restriction are separate. The implications of these findings to the relationship between idiotypic elements, antigen-binding structures, and Igh restriction elements on immunoregulatory T cells are discussed.

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

Complete amino acid sequence of heavy chain variable regions derived from two monoclonal anti-p-azophenylarsonate antibodies of BALB/c mice expressing the major cross-reactive idiotype of the A/J strain.

The primary structure of A/J anti-p-azophenylarsonate (anti-Ars) antibodies expressing the major A-strain cross-reactive idiotype (CRIA) has provided important insights into issues of antibody diversity and the molecular basis of idiotypy in this important model system. Until recently, this idiotype was thought to be rarely, if ever, expressed in BALB/c mice. Indeed, it has been reported that BALB/c mice lack the heavy chain variable segment (VH) gene that is utilized by the entire family of anti-Ars antibodies expressing the A/J CRI. Recently, however, it has been possible to elicit CRIA+, Ars binding antibodies in the BALB/c strain by immunizing first with anti-CRI and then with antigen. Such BALB/c, CRIA+ anti-Ars antibodies can be induced occasionally with antigen alone. VH region amino acid sequences are described for two CRIA+ hybridoma products derived from BALB/c mice. While remarkably similar to each other, their VH segments (1-98) differ from the VH segments of A/J CRIA+, anti-Ars antibodies in over 40 positions. Rather than the usual JH2 gene segment used by most A/J CRIA+ anti-Ars antibodies, one BALB/c CRIA+ hybridoma utilizes a JH1 gene segment, while the other uses a JH4. However, the D segments of both of the BALB/c antibodies are remarkably homologous to the D segments of several A/J CRIA+ antibodies sequenced previously, as are the amino terminal amino acid sequences of their light chains. These data imply that BALB/c mice express the A/J CRIA by producing antibodies with very similar, if not identical, light chain and heavy chain D segments, but in the context of different VH and JH gene segments than their A/J counterparts. The results document that molecules that share serologic specificities can have vastly different primary structures.

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

Idiotypic studies of monoclonal anti-tobacco mosaic virus antibodies from one mouse.

Monoclonal antibodies have been prepared from one BALB/c mouse immunized with tobacco mosaic virus. The monoclonal antibodies are distributed into three subgroups recognizing different epitopes on tobacco mosaic virus subunits. The idiotypic specificities of these monoclonal antibodies have been studied using syngeneic antiidiotypic sera. A sharing of idiotypic specificities has been observed between members of each subset. These idiotypes are not recurrent in BALB/c mice immunized with tobacco mosaic virus.

Animals↗
PubMedDate not supplied

An in vitro method using vascular smooth muscle cells to study the effect of compounds on cell proliferation and intracellular lipid accumulation.

Primary cultures of vascular smooth muscle cells (SMC) were incubated with hyperlipidemic rabbit serum (HLRS) to produce intracellular lipid accumulation. Cultures were exposed to different concentrations of the test compounds and their effects upon cell proliferation and intracellular lipid accumulation were measured. The in vitro results obtained with different Ca2+ antagonists, a HMG-CoA reductase inhibitor and other hypolipidemic substances showed a strong correlation with the in vivo activities of these compounds, suggesting that cultured SMC may be a useful initial in vitro model to detect new chemical entities active upon atherosclerosis related parameters.

Animals↗