Einstein (Sao Paulo, Brazil) · 2024
Severe murine schistosomiasis results from disrupted CD4+ T-cell modulation by immunodominance of a single egg epitope.
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Finger Eduardo, Coimbra Thaissa Melo Galante, Dastoli Alessandra Finardi
Аннотация
OBJECTIVE: This study examined the correlation between immunodominance of the major egg antigen Sm-p40234-246, a robust Th1/Th17 anti-egg CD4 T-cell response, and severe liver immunopathology in experimental murine schistosomiasis. It serves as a platform to analyze how varying degrees of immunodominance affect CD4+ T cell modulation and disease outcomes.
METHODS: We used a murine model of schistosomiasis to investigate the effects of immunodominance. Infected mice were divided into two groups: one treated with a combination of epitopes targeting immunodominance of the major egg antigen Sm-p40 and the other with a mock mixture of non-immunogenic epitopes. Liver granuloma area, a hallmark of schistosomiasis pathology, was quantified using histological and morphometric analyses. The average granuloma areas between the treated and untreated groups were compared using one-way ANOVA with Tukey's multiple comparison test. Additionally, we isolated CD4+ T cells from mesenteric lymph nodes, stimulated them with specific egg antigens, and collected purified supernatants to assess their signature cytokine secretion profiles for each treatment group.
RESULTS: Results showed that strong immunodominance of a single egg epitope undermines effective CD4+ T-cell modulation, promoting a strongly polarized Th1/Th17 pathogenic response. Conversely, neutralizing this immunodominance produces the opposite restorative effect.
CONCLUSION: Immunodominance is an important pathogenic component that influences CD4+ T cell modulation in experimental murine schistosomiasis. Moreover, immunodominance can be used to treat these and other important CD4+ T cell-mediated diseases.
METHODS: We used a murine model of schistosomiasis to investigate the effects of immunodominance. Infected mice were divided into two groups: one treated with a combination of epitopes targeting immunodominance of the major egg antigen Sm-p40 and the other with a mock mixture of non-immunogenic epitopes. Liver granuloma area, a hallmark of schistosomiasis pathology, was quantified using histological and morphometric analyses. The average granuloma areas between the treated and untreated groups were compared using one-way ANOVA with Tukey's multiple comparison test. Additionally, we isolated CD4+ T cells from mesenteric lymph nodes, stimulated them with specific egg antigens, and collected purified supernatants to assess their signature cytokine secretion profiles for each treatment group.
RESULTS: Results showed that strong immunodominance of a single egg epitope undermines effective CD4+ T-cell modulation, promoting a strongly polarized Th1/Th17 pathogenic response. Conversely, neutralizing this immunodominance produces the opposite restorative effect.
CONCLUSION: Immunodominance is an important pathogenic component that influences CD4+ T cell modulation in experimental murine schistosomiasis. Moreover, immunodominance can be used to treat these and other important CD4+ T cell-mediated diseases.