Induction of antibodies against the Plasmodium falciparum p126 antigen in non-responder H-2b and partial-responder H-2d mice using synthetic peptides.

The p126 Plasmodium falciparum antigen is processed into two fragments, p50 and p73, the latter one containing the subfragments p47 and p18 when the schizonts rupture. An absence of antibody response against the p126 antigen has been reported recently in H-2b mice and limited to the p73 processed fragment in H-2d mice. Synthetic peptides corresponding to various domains of the molecule have been used to immunize mice in order to overcome the absence of an immune response.

Improvement of the T-cell response to a non immunogenic peptide by its tandem association with a highly efficient T-helper peptide.

The 45-69 peptide, an helper T-cell epitope derived from the HIV nef protein is strongly immunogenic. A T-cell proliferative response was observed following immunization of Lou/M rats with 45-69 peptide administered in low dose and without any adjuvant. It is already known that the T-cell response to the 115-131 peptide of Sm28GST antigen, a protein of the parasite Schistosoma mansoni, requires the presence of a carrier of the use of peptidic constructs.

Effect of a lipopeptidic formulation on macrophage activation and peptide presentation to T cells.

We studied a 45-69 lipopeptide obtained by N-terminal modification with a N epsilon-palmitoyl lysine residue of the 45-69 peptide derived from the nef protein of HIV. T cells from animals immunized intraperitoneally with 45-69 lipopeptide proliferated in vitro in the presence of 45-69 peptide while no response was obtained after intraperitoneal immunization with 45-69 peptide. The efficiency of the 45-69 lipopeptide is supported by the covalent association to the N epsilon-palmitoyl lysine moiety.

Improvement of the T-cell response to a non-immunogenic peptide by its tandem association with a highly efficient T-helper peptide.

The 45-69 peptide, an helper T-cell epitope derived from HIV nef protein, is strongly immunogenic. A T-cell proliferative response was observed following immunization of Lou/M rats with 45-69 peptide administered in low dose and without any adjuvant. It is already known that the T-cell response to the 115-131 peptide of Sm28GST antigen, a protein of the parasite Schistosoma mansoni, requires the presence of a carrier or the use of peptidic constructs.

H-2b restriction of the immune response to the p126 Plasmodium falciparum antigen.

Inbred BALB/c (H-2d), CBA (H-2k) and C57B1/6 (H-2b) mice immunized with Plasmodium falciparum schizonts or culture supernates develop antibodies of different antigenic specificities. It has been observed that C57B1/6 mice were unable to produce detectable antibodies against the p126 antigen (native molecule and p73 or p50 processed fragments) compared with other inbred mice. Similar results were obtained using BALB congenic mice with a lack of p126 antibody response in H-2b mice, while H-2d and H-2k mice produced antibodies against the p126.

Analysis of antigenicity and immunogenicity of five different chemically defined constructs of a peptide.

The aim of this study was to compare the antigenicity and the immunogenicity of five constructs of a peptide, including the peptide in single copy, a tandem repeat containing three copies, a copolymer with glutaraldehyde and two constructs based on the MAP (Multiple Antigenic Peptide) model, one containing two copies (MAP-2) and the other, eight copies of the peptide (MAP-8). The peptide used in this test was the 115-131 sequence derived from the rSm28-GST antigen of Schistosoma mansoni. All constructs were recognized by rSm28-GST specific antibodies in solid phase immunoassays.

Immunogenicity and antigenicity of the N-term repeat amino acid sequence of the Plasmodium falciparum P126 antigen.

The P126 protein, a parasitophorus vacuole antigen of Plasmodium falciparum has been shown to induce protective immunity in Saimiri and Aotus monkeys. In the present work we investigated its immunogenicity. Our results suggest that the N-term of P126 is poorly immunogenic and the antibody response against the P126 could be under a MHC restricted control in C57BL/6(H-2b) mice, which could be problematic in terms of a use of the P126 in a vaccine program.

Functional analysis of a T cell line specific for antiidiotypic antibodies to a Schistosoma mansoni protective epitope. I. Role in the anti-S. mansoni antibody response.

Previous data have shown that from an antiparasitic IgE mAb (mAb1), antianti-Id IgG and IgE antibodies (Ab3) could be prepared. These Ab3 demonstrated the same functional properties as the Ab1, such as in vitro cytotoxic activity toward schistosomula and in vivo a protective effect against Schistosoma mansoni infection. To study the possible interactions between the idiotypic network and the regulation of isotypic expression, we focused on Id-specific T cells obtained by immunization with Ab2.

Obtention of a human primary humoral response against schistosome protective antigens in severe combined immunodeficiency mice after the transfer of human peripheral blood mononuclear cells.

Peripheral blood mononuclear cells (PBMC) from healthy donors were injected into C.B.-17 severe combined immunodeficiency (scid) mice which were subsequently immunized with crude Schistosoma mansoni adult worm antigenic preparation (SWAP) or with recombinant S.

Antigenicity and immunogenicity of a multiple peptidic construction of the Schistosoma mansoni Sm-28 GST antigen in rat, mouse, and monkey. 1. Partial protection of Fischer rat after active immunization.

Among the schistosome proteins characterized as vaccine candidates, an Ag of 28 kDa (Sm-28-GST) has received considerable attention. It was shown to be antigenic in humans and protective in mice, rats, hamsters, and baboons. Synthetic peptides derived from its sequence have been used to characterize the immune response to the molecule and one of these, comprising aminoacids 115-131 has been shown to incorporate both T and B cell recognition sites in a variety of experimental models.

T-cell responsiveness towards various synthetic peptides of the P28 antigen in rat and mouse models during Schistosoma mansoni infection.

It has recently been demonstrated that the Schistosoma mansoni P28 antigen can induce a strong protective immunity after direct immunization in various experimental models. T lymphocytes from Fischer rats immunized with the recombinant P28 antigen were cultured in vitro in the presence of seven synthetic peptides derived from the amino acid sequence of the P28. The most significant and reproducible proliferation was obtained with the 24-43 and 115-131 synthetic peptides.

In vitro and in vivo effects of interleukin 2 on the protozoan parasite leishmania.

T cells can have either resistance-promoting or disease-promoting effects in murine cutaneous leishmaniasis. It is known that the adoptive transfer of parasite-specific helper T cells led to an exacerbation of Leishmania-induced lesions. This work presents evidence that lymphokines produced by activated T cells could be involved in this exacerbating process by directly stimulating the parasite growth.

Induction of platelet cytotoxic functions by lymphokines: role of interferon-gamma.

Antigen- or mitogen-stimulated CD4+/CD- lymphocytes produced factors able to induce normal human platelets into cytotoxic effectors toward the young larvae of Schistosoma mansoni. The neutralization by monoclonal anti-IFN-gamma antibody of the induction of the platelet killer effect, the presence of IFN-gamma in the CD4+/CD8- lymphocyte supernatant, and, finally, the direct inducer effect of recombinant IFN-gamma clearly demonstrated that IFN-gamma was one of the factors responsible for the induction of platelet cytotoxic functions.

Regulation of IgE synthesis by macrophages expressing FcE-receptors: role of interleukin 1.

Triggering rat macrophages with IgE complexes induced the production of interleukin 1-like activity (IL-1). The signal is delivered through the macrophage FcE receptor since stimulating macrophages with IgE bound to spleen cells (to avoid endocytosis) or with an anti-FcE receptor antibody linked to nonphagocytizable cells also led to IL-1 production. The molecular weight of IL-1 produced after IgE triggering is in the same range (30 kD) as previously described for rat IL-1.

Effect of schistosome-derived inhibitory factor on the cell cycle of T lymphocytes.

A schistosome-derived inhibitory factor (SDIF) with immunosuppressive properties has been investigated for its effect on human T cell proliferation. We show here that SDIF has no effect on the process of lymphocyte activation because peripheral blood leukocytes (PBL) stimulated with lectin in the presence of SDIF increased normally their RNA content and showed normal acquisition of interleukin 2 (IL-2) and transferrin receptors. IL-2 production was not altered by SDIF but utilization of IL-2 was decreased, suggesting that SDIF blocked cells before or in the early s phase.

Schistosome-derived inhibitory factor: an immunosuppressive agent preferentially active on T lymphocytes.

We have previously shown that schistosome-derived inhibitory factors (SDIF) inhibited lymphocyte proliferation and induced immunosuppression. Crude SDIF was purified by successive gel filtration and reverse-phase high-performance liquid chromatography. Purified SDIF preparations strongly inhibited the proliferation of different T cell line cells, while other cell lines (B cells, macrophages and fibroblasts) were almost not affected by SDIF.

Non-specific potentiation of T- and B-lymphocyte proliferation at the early stage of infection by Schistosoma mansoni: role of factors secreted by the larvae.

The response of rat lymphocytes to schistosomula released products (SRP) was examined. SRP non-specifically activated lymphocytes by potentiating their proliferative response to PHA, Con A or LPS. The parasite factor involved was dialysable and heat stable.

Inhibition of primary and secondary IgE-response by a schistosome-derived inhibitory factor.

Schistosome-derived inhibitory factor (SDIF) previously shown to inhibit lymphocyte proliferation, markedly decreased the primary IgE response of rats immunized with dinitrophenylated ovalbumin (DNP-OVA) when injected either simultaneously or shortly after antigen administration. No effect however was observed when SDIF was injected before the immunization. An inhibition of non-IgE anti-DNP antibodies was also found in SDIF-treated rats although the decrease was lower than with IgE antibody.

Inhibition of cytotoxic T lymphocytes by a schistosome-derived inhibitory factor is independent of an inhibition of the production of interleukin 2.

Schistosome-derived inhibitory factor (SDIF) was shown to inhibit lymphocyte proliferation. While SDIF is not toxic to lymphoid cells, the generation of cytotoxic effector cells was inhibited by SDIF in a mixed lymphocyte culture. This inhibitory effect was not attributable to the induction of suppressor cells, as SDIF also inhibited the development of nonspecific suppressor cell activity in 7-day cultures of unstimulated spleen cells.

Immunoregulation by Schistosoma mansoni.

Schistosoma mansoni is known to release an inhibitory factor of lymphocyte proliferation elicited in vitro. The effect of this dialyzable schistosome incubation product (DSIP) was tested in vivo on different aspects of the cell-mediated immune response. First, the DSIP injected into C57B1/6 mice markedly inhibited the delayed type hypersensitivity to sheep red blood cells (SRBC).

Rat mast cell-eosinophil interaction in antibody-dependent eosinophil cytotoxicity to Schistosoma mansoni schistosomula.

The involvement of IgG2a antibodies and mast cells in antibody-dependent eosinophil cytotoxicity suggested a possible interaction between mast cells and eosinophils for in vitro killing of Schistosoma mansoni schistosomula. Cell purification procedures showed that a minimum ratio of mast cells was required to obtain eosinophil cytotoxicity. The incubation of mast cells with heat-aggregated IgG2a immunoglobulins before addition to a mast cell-depleted eosinophil population induced a significant degree of inhibition of cytotoxicity, Similarly, the heat-aggregated IgG2a Fc fragment had a strong inhibitory effect whereas incubation of mast cells with Fab fragment failed to inhibit the cytotoxic effect.

[3H]serotonin release: an improved method to measure mast cell degranulation.

A method based on the release of tritium-labelled serotonin by activated mast cells in rodents is described. Mast cells incorporate labelled serotonin selectively and release the label after activation by non-specific stimulators (compound 48/80, polymyxin B sulphate, ATP, bovine chymotrypsin and L-alpha-lysophosphatidylcholine) or anaphylactic antibody and the corresponding antigen. These two types of activation were investigated in comparison with the toluidine blue microscopic rat mast cell degranulation test, and a methodological study of the release of [3H]serotonin is described.