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Updated: Jan 1, 2026
Quantitative 3D Imaging of Trypanosoma cruzi-Infected Cells, Dormant Amastigotes, and T Cells in Intact Clarified Organs
Published on: June 23, 2022
Diminished mitogen-induced T cell proliferation by Trypanosoma cruzi antigens associated with antigen-presenting cell
Sergio Gómez-Olarte1, Natalia I Bolaños2, Adriana Cuéllar3
1Grupo de Ciencias Básicas Médicas, School of Medicine, Universidad de los Andes, Bogotá, Colombia; Department of Biological Sciences, School of Sciences, Universidad de los Andes, Bogotá, Colombia.
Abstract:
Chronic infection by Trypanosoma cruzi decreases T cell proliferation and it is most likely accompanied by changes in signals required for activation. We assessed the effect of T. cruzi antigens on mitogen-induced proliferation of T cells from uninfected individuals and the association with the expression of molecules involved in antigen presentation, T cell costimulation and activation, and cytokine production. T. cruzi antigen exposure reduced mitogen-induced proliferation of CD4+ and CD8+ T cells in PBMC cultures, but only reduced mitogen-induced proliferation in the CD4+ T cells from sorted cell cultures cocultured with antigen-pulsed CD3- cells. CD40/CD80 and CD86 expression were reduced in antigen-pulsed DCs and monocytes, respectively. TNF-α, IL-10 and CCL17 levels were increased in cultures with antigen-pulsed CD3- cells, while CD3ζ chain expression was reduced in T cells from cultures with antigen. Our findings suggest that T. cruzi could alter T cell proliferation indirectly by downregulating costimulatory molecules and inducing the secretion of IL-10 and directly by decreasing TCR signaling.
Insights
Trypanosoma cruzi antigens impair T cell proliferation by reducing costimulatory molecules and decreasing T cell receptor signaling. This chronic infection impacts immune responses, affecting T cell activation and cytokine production.
Area of Science:
- Immunology
- Infectious Diseases
- Cell Biology
Background:
- Chronic Trypanosoma cruzi infection is known to suppress T cell responses.
- Understanding the precise mechanisms of T cell dysfunction during infection is crucial for developing therapeutic strategies.
Purpose of the Study:
- To investigate the impact of Trypanosoma cruzi antigens on T cell proliferation and activation markers.
- To elucidate the role of antigen presentation, costimulatory molecules, and cytokine production in T cell response modulation.
Main Methods:
- Peripheral blood mononuclear cells (PBMCs) and sorted T cells from healthy donors were exposed to T. cruzi antigens.
- Mitogen-induced T cell proliferation assays were performed.
- Expression of costimulatory molecules (CD40, CD80, CD86) on antigen-presenting cells and T cell activation markers (CD3ζ chain) were analyzed.
- Cytokine levels (TNF-α, IL-10, CCL17) were measured.
Main Results:
- T. cruzi antigens reduced mitogen-induced proliferation of both CD4+ and CD8+ T cells in PBMCs.
- Reduced proliferation was observed in sorted CD4+ T cells when co-cultured with antigen-pulsed CD3- cells.
- Expression of CD40/CD80 and CD86 was decreased on antigen-pulsed dendritic cells and monocytes, respectively.
- Levels of TNF-α, IL-10, and CCL17 increased, while CD3ζ chain expression decreased in T cells exposed to antigens.
Conclusions:
- Trypanosoma cruzi antigens can indirectly impair T cell proliferation by downregulating costimulatory molecules and promoting IL-10 secretion.
- Directly, antigens may decrease T cell proliferation by reducing T cell receptor (TCR) signaling, indicated by decreased CD3ζ chain expression.
- These findings highlight multifaceted immune evasion strategies employed by T. cruzi.
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