HLA class II polymorphism influences onset and severity of pathology in Schistosoma mansoni-infected transgenic mice.

Genetic factors that might influence susceptibility or resistance in naive individuals and early-stage pathology in schistosomiasis are difficult to study in clinical trials, since in areas where the disease is endemic the first contact with the parasite occurs most often at very early ages. Therefore, four strains (DR1.Abeta degrees, DR2.Abeta degrees, DQ8.Abeta degrees, and DQ6.Abeta degrees ) of major histocompatibility complex class II-deficient mice (Abeta degrees ), transgenic for different HLA alleles, have been used to evaluate the potential role of HLA class II polymorphism in the onset of the infection by Schistosoma mansoni. The survival rates and parasitological and immunological parameters after infection were evaluated and compared against the control values obtained with Abeta degrees mice. All four mouse strains used in this study were able to generate a specific immune response against S. mansoni antigens (cytokine production and antibody production). However, only mice expressing DR alleles survived until the chronic stage of the infection and were able to mount protective granulomatous response avoiding hepatic damage, presenting predominant gamma interferon production. In contrast, strains expressing DQ alleles revealed an impairment in generating effective granulomas, resulting in earlier death, which was associated with an impaired hepatic granulomatous response and liquefactic necrosis, reflecting the influence of HLA polymorphism in the establishment of protective response in the early stage of infection.

Schistosomal egg antigen-responsive CD8 T-cell population in Schistosoma mansoni-infected BALB/c mice.

We demonstrated here that schistosomal egg antigen (SEA) is able to stimulate an antigen-specific, cytotoxic CD8+ T-cell response in mice. Indeed, a single i.p. immunization with SEA resulted in the in vivo induction of significant cytotoxic T lymphocyte (CTL) activity in the spleen within 20 days. Effector cells were classic class I major histocompatibility complex (MHC)-restricted CD8+ lymphocytes producing interferon-gamma (IFN-gamma) and interleukin-2 (IL-2), suggesting a type 1 response to SEA. We therefore investigated the relevance of these observations in the context of the Schistosoma mansoni parasite infection. CTL activity against SEA-pulsed target cells was evidenced throughout the infection after in vitro stimulation of recovered splenic cells with SEA demonstrating that SEA-specific CD8+ T cells with cytotoxic potentialities are present during infection. This activity was strongly increased after immunization of mice with SEA like the production of IFN-gamma in the sera. A marked reduction in the number of granulomas and of fibrosis with the presence of cells producing IFN-gamma in the liver was also observed leading to the survival of SEA-immunized mice.

Immunological response of major histocompatibility complex class II-deficient (Abeta(o)) mice infected by the parasite Schistosoma mansoni.

We have characterized the immunological behaviour of major histocompitibility complex (MHC) Class II molecule-deficient (Abeta(o)) mice after infection by Schistosoma mansoni. In Abeta(o) mice, morbidity developed dramatically 7 weeks after infection leading to death, despite the absence of an increase in parasite burden or of eggs trapped in the liver. Histological examination of the liver revealed the absence of a classical granulomatous reaction. Antibodies were produced only against schistosomulum antigens. Specific antibodies against adult worm (SWAP) or egg antigen (SEA) were not detected. Cytokine production (IFN-gamma and IL-4) was absent after in vitro restimulation of splenic cells from infected Abeta(o) mice with parasite antigens. Adoptive transfer of primed splenic cells (total, purified CD4+ or CD8+ T cells) failed to improve survival or to induce a granulomatous reaction in infected Abeta(o) mice. Survival, cellular and humoral responses in CD8+ T-cell-depleted Abeta(o) mice or MHC(o) mice (lacking MHC class I and II molecules) were similar to nondepleted Abeta(o) mice, suggesting that anti-schistosomula antibody production was thymo-independent. Our results demonstrate a high degree of susceptibility of Abeta(o) mice to infection and corroborate the importance of CD4+ T cells in the initiation of the granulomatous response. However, our results do not show evidence for the involvement of CD8+ T cells in response to S. mansoni infection.

Induction of cytotoxic T-cell activity by the protective antigen of Schistosoma mansoni Sm28GST or its derived C-terminal lipopeptide.

In a previous work the authors demonstrated that immunization with Schistosoma mansoni 28-kDa glutathione-S-transferase (Sm28GST) was able to reduce hepatic damage in infected mice and that the adoptive transfer of Sm28GST-specific T cells reproduced the protective effect obtained with the recombinant molecule. In the present paper, the authors show that Sm28GST is also able to stimulate an antigen-specific, cytotoxic T-cell response against Sm28GST-pulsed P815 target cells in normal mice and that effector cells induced in vivo were classical Class I MHC-restricted CD8+ lymphocytes. The authors found no spontaneous CTL activity against Sm28GST-pulsed target cells during the course of the infection by S. mansoni although Sm28GST is expressed at different developmental stages of the parasite. It was observed, however, that immunization with Sm28GST is sufficient to elicit a significant level of CTL response for 6 weeks in infected mice. The role of these Class I MHC-restricted CD8+ lymphocytes in the protection observed precisely at the same period in immunized mice remains to be elucidated. The authors also observe that immunization with the lipopeptide form of the C-terminal peptide of the molecule (190-211 peptide) led to a CTL activation comparable to that observed after immunization with the whole molecule demonstrating the feasibility of using a synthetic lipopeptide as immunogen for a CTL response against Sm28GST epitopes. Moreover, like Sm28GST-specific CTLs, 190-211 lipopeptide-specific cells were also Class I MHC-restricted lymphocytes.

Studies on the incidence of rat ileocecal malignant immunocytoma: vertical transmission of the high tumour incidence.

Monoclonal immunoglobulin-secreting tumours (immunocytomas, myelomas or plasmocytomas) appear with a high or low incidence in 2 sublines, LOU/C and LOU/M respectively, of the same inbred strain of rats. Studies of the reciprocal hybrids of the first generation between both substrains have shown that the transmission of the high tumour incidence from parents to offsprings is determined by the male as well as by the female. Absence of C-type viral particles in LOU/C rats and immunocytomas derived from them suggests that this vertical transmission might be genetically mediated.