Abstract
The pathogenesis of chronic chagasic cardiomyophathy associated with Chagas disease is still controversial, although evidence indicates a T cell-dependent autoimmune process. Using a mouse model for chronic Chagas disease, we previously evidenced that hearts grafted within the ears of Trypanosoma cruzi infected syngeneic recipients were rejected through a CD4+ T cell-dependent mechanism. Moreover, we showed that such a process was dependent on laminin-mediated interactions, since it could be abrogated by anti-laminin or anti-laminin receptor antibodies. In this review the same passive cell transfer model is considered for discussion: the participation of the laminin alteration in the composition of the inflammatory infiltrate formed in response to the antimyocardial autoreactive CD4+ T cells, as well as the presence of laminin-binding cytokines. Finally we suggest the existence of a relationship between the inflammatory infiltrate, the laminin contents and deposition of pro-inflammatory laminin-binding cytokines, which may act in concert during the generation of Chagas disease-related cardiomyophathy.
Figures
![FIGURE 3 Hypothetical scheme on the mechanisms involved in heart graft rejection mediated by CD4 T cells from chagasic mice. Panel a depicts a heart transplanted area before injection of splenic CD4 T cells derived from infected mice, showing the distribution of myoblast cells, resident fibroblasts and macrophages, laminin and myoblast antigens. Injection of CD4 cells from infected mice (in red) can convey the local production of IFN-,. Additionally, IFN-qt is possibly up-regulating laminin production by stromal cells and/or cardiomyocytes (panel b). Once laminin content is locally augmented, it favors cell arrival, so that the leukocyte recruitment triggered by IFN-], should be further enhanced, through the well defined haptotatic effect of this ECM protein. Moreover, IFN-qt can activate macrophages to produce TNF- and increase their expression of MHC gene products (panel c). In response to the transplantation process and/or injection of CD4 cells, cardiac antigens can be exposed and presented by local antigen presenting cells. On the other hand, the binding of IFN-qt and TNF- to laminin, not only increases their local concentrations, but also favor the activation of resident macrophages. This is relevant in the context discussed herein, since the presence of activated TNF- secreting macrophages, can also act upon endothelial cells, increasing the expression of adhesion molecules and recruiting circulating cells from the recipient animal. Conjointly, these stimuli would amplify and maintain the cardiac inflammatory lesion. Since the in vivo treatment with anti-laminin mAb revealed a progressive decrease in cell infiltration associated with a diminished deposition of laminin and laminin-binding inflammatory cytokines, such a treatment would, not only decrease the intragraft influx of CD4 cells, but also diminish the secretion/sequestration of IFN-7 and TNF-c, as compared to the pattern observed in rejecting control heart grafts (see Color Plate XXII at the back of this issue)](https://s3-eu-west-1.amazonaws.com/com.mendeley.prod.article-extracted-content/images/4f4126eb-db6d-3fba-af3e-fb667b7983eb/thumbnail-dee78ede-a0b3-4c3e-818c-0a36bce6a727-1.png)
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CITATION STYLE
Silva-Barbosa, S. D., & Savino, W. (2000). The involvement of laminin in anti-myocardial cell autoimmune response in murine chagas disease. Developmental Immunology, 7(2–4), 293–301. https://doi.org/10.1155/2000/17424
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