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A 24,000 MW Trypanosoma cruzi antigen is a B-cell activator
A C Da Silva1, A G Espinoza, A Taibi
1Department of Immunology, Pasteur Institute, Paris, France.
Insights
A recombinant Trypanosoma cruzi antigen (rTc24) stimulates B-cell activation and proliferation in mice. This antigen promotes increased IgM-secreting B cells and immunoglobulin levels, suggesting a role in B-cell immune responses.
Area of Science:
- Immunology
- Parasitology
- Molecular Biology
Background:
- Chagas' disease, caused by Trypanosoma cruzi, leads to immune dysregulation, including immunosuppression and polyclonal lymphocyte activation.
- Understanding immune responses to specific parasite antigens is crucial for developing effective interventions.
Purpose of the Study:
- To investigate the immunomodulatory effects of a recombinant Trypanosoma cruzi antigen (rTc24) in mice.
- To determine the impact of rTc24 on lymphocyte activation, proliferation, and antibody production.
Main Methods:
- Intraperitoneal injection of rTc24 in normal and immunodeficient mouse strains.
- Analysis of lymphocyte activation markers (CD69) and proliferation ([3H]thymidine incorporation).
- Quantification of antibody-producing cells (ELISPOT) and serum immunoglobulin levels (ELISA).
Main Results:
- rTc24 induced significant spleen cell proliferation in vitro and in vivo, independent of mouse strain.
- rTc24 preferentially activated B cells, evidenced by increased CD69 expression on IgM+ cells.
- Elevated numbers of IgM-secreting B cells and serum IgM levels were observed in rTc24-treated mice.
Conclusions:
- The recombinant Trypanosoma cruzi antigen rTc24 possesses potent B-cell activating properties.
- rTc24 induces a specific IgM-mediated humoral immune response.
- These findings suggest a potential role for rTc24 in modulating B-cell immunity during T. cruzi infection.
Abstract:
Trypanosoma cruzi, the causative agent of Chagas' disease, is a protozoan parasite that infects humans and other mammals in Central and Latin America. Several alterations of the immune response after infection have been described, such as severe immunosuppression of both cellular and humoral responses and massive polyclonal B- and T-cell activation, including the expansion of self-reactive clones. We have investigated the effects of the intraperitoneal injection of a recombinant 24,000 MW T. cruzi-specific antigen (rTc24) on the immune response of normal and deficient strains of mice. We analysed the in vivo and ex vivo levels of lymphocyte activation and the proliferative responses to rTc24 by determining the expression of CD69 activation marker and the levels of thymidine incorporation by spleen cells. The numbers of antibody-producing cells were determined by ELISPOT and the levels of immunoglobulin in the sera by isotype-specific enzyme-linked immunosorbent assay. We observed an increased [3H]thymidine ([3H]TdR) incorporation by spleen cells after rTc24 stimulation in vivo and in vitro. This proliferative activity induced by rTc24 was independent of the mouse strain used in the experiments (including C3H/HeJ mice) and ruled out the possibility that rTc24 preparations were contaminated by lipopolysaccharide. The injection of rTc24 protein induced preferentially the activation of B cells, as determined by the increased expression of CD69 molecules on IgM+ spleen cells. Considerable increases of IgM-secreting B cells were determined in both athymic and euthymic BALB/c mice. Mice that are deficient in B cells (BALB.Xid) responded to rTc24 but to a lesser extent. These increases in IgM B-cell numbers were accompanied by elevated levels of IgM immunoglobulins in the sera of injected animals. Our results suggest a role for rTc24 in B-cell activation.
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