Infection of B-cell-deficient mice by the parasite Schistosoma mansoni: demonstration of the participation of B cells in granuloma modulation.

The contribution of B lymphocytes to immunity towards the parasite Schistosoma mansoni has been investigated in a mouse strain rendered genetically B-cell deficient (the muMT mouse). These studies demonstrated that T cells primed in vivo in B-cell-deficient mice proliferate less efficiently in vitro in response to parasite antigenic extracts except at 10 weeks of infection. In addition, analysis of the cytokine profiles (IL-2, IL-4, IL-5 and IFN-gamma), investigated using RT-PCR, showed that spleens of muMT animals displayed a predominant Th1-like profile compared to control, B-cell-intact infected mice. This showed that B cells, either per se or through their secretions, are involved in the in vivo generation and/or maximal expansion of Th2-type T lymphocytes during the course of murine S. mansoni infection. Interestingly, the data showed that B-cell-deficient mice display an increased hepatic fibrosis at 10 weeks postinfection (p.i.), whereas they behaved like infected controls, with regard to the other assessed parasitological parameters (e.g. worm burden estimation). This demonstrated that even if B lymphocytes are not essential for the development of the general immune response towards S. mansoni in the mouse, they may nevertheless be involved in the correct immunoregulation of the granulomatous reaction around the eggs.

Analysis of the immune response elicited by a multiple antigen peptide (MAP) composed of two distinct protective antigens derived from the parasite Schistosoma mansoni.

In this report we analyse the immune response elicited by a Multiple Antigen Peptide (MAP), containing three peptide sequences derived from two distinct vaccine candidates against schistosomiasis; the Schistosoma mansoni 28 kDa Gluthatione-S-Transferase (Sm28GST) and the Schistosoma mansoni Triose-Phosphate-Isomerase (sTPI). We examined the immunogenicity of this construct, named MAP 'DA', in three distinct mouse strains. The B-cell response, studied by measuring the production of different IgG isotypes, was mainly directed against the peptide derived from the Sm28GST, but also against the whole Sm28GST protein. In contrast, the T-cell response, as assessed by proliferation assay and cytokine mRNA expression, was directed against the MAP construct, the peptides derived from the sTPI protein and the whole sTPI protein. Significantly, T-cells from all MAP 'DA'-immunized mice, restimulated in vitro was the sTPI antigen, expressed IFN-gamma specific messengers. This cytokine has been described to play a major role in the reduction of the Schistosoma mansoni pathology. We thus demonstrate that a single MAP construct, composed of peptides from distinct antigens of Schistosoma mansoni, induced a B- and T-cell response, including production of potentially protective IFN-gamma, irrespective of the MHC background.

Cellular immune response and pathology in schistosomiasis.

In the present review, some aspects of the cellular response following the murine Schistosoma mansoni infection are described. Due to the peculiar route used by the schistosome to infect its definitive host, the skin appears as a critical site in which the initial events of the host/parasite relationship occur and where the immune response is initiated. Moreover, the induction and the modulation of the granuloma formation, which represent the main aspect of the pathology of this parasitic disease, is under the control of several cellular populations n which CD4 and CD8 T cells play a key role. The cytokines produced in response to the parasite, such as IL7 in the skin and IFN gamma in the liver, seem to influence the further development of immunity against Schistosoma mansoni.

Comparison of the immune response elicited by a free peptide and a lipopeptide construct.

Among the synthetic peptides derived from the 28-kDa Schistosoma mansoni gluthatione-S-transferase (Sm28GST), the C-terminal peptide, comprising amino acid residues 190 to 211, represents a major T-cell epitope in both infected humans and Sm28GST-immunized mice. The aim of this study was to determine the nature of the immune response induced by the 190-211 peptide coupled to a fatty acid (lipopeptide construction) in comparison to the free form. We explored B- and T-cell responses elicited by these two peptidic constructions in three different mouse strains (BALB/c, CBA/N and C57B1/6). For all strains, the addition of a lipid chain to the 190-211 peptide greatly modified its immunogenicity. The lipopeptide, compared to the free form, induced a greatly reduced antibody response against the peptide, whereas the production of messenger for cytokines was greatly increased after immunization with the lipopeptide. Immunization with peptide led mainly to a Th1-type cytokine profile following antigenic restimulation in vitro, while lipopeptide, in general, induced a mixed profile, and that occurred most significantly with the production of messengers for the protective cytokines IFN-gamma and IL-2, even without antigenic restimulations. This modification of immunogenicity of a peptide by the addition of a lipid chain could be of value in the development of efficient peptide vaccines.