Understanding CD8+ T Cell Immunity to Trypanosoma cruzi and How to Improve It

• Published in: Trends in parasitology Vol. 35; no. 11; pp. 899 - 917
• Main Authors: Acosta Rodríguez, Eva V., Araujo Furlan, Cintia L., Fiocca Vernengo, Facundo, Montes, Carolina L., Gruppi, Adriana
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.11.2019
• Subjects: CD8+ T cells; Chagas' disease; Trypanosoma cruzi; CD8+ T cells; Chagas' disease; Trypanosoma cruzi; CD8(+) T cells
• ISSN: 1471-4922; 1471-5007
• DOI: 10.1016/j.pt.2019.08.006

The protozoan Trypanosoma cruzi is the causative agent of Chagas' disease, endemic in Latin America but present worldwide. Research efforts have focused on the examination of immune mechanisms that mediate host protection as well as immunopathology during this parasitic infection. The study of CD8+ T cell immunity emerges as a key aspect given the critical importance of parasite-specific CD8+ T cells for host resistance throughout the infection. In recent years, new research has shed light on novel pathways that modulate the induction, maintenance, and regulation of CD8+ T cell responses to T. cruzi. This new knowledge is setting the ground for future vaccines and/or immunotherapies. Herein, we critically review and analyze the latest results published in the field. CD8+ T cells are critical for host resistance during T. cruzi infection given their effectiveness to control parasite outgrowth throughout all infection stages.T. cruzi-specific CD8+ T cell immunity shows a significant magnitude but develops with delayed kinetics, displays a relatively reduced breadth, and may acquire dysfunctional features.Proliferation, survival, and cell exhaustion of T. cruzi-specific CD8+ T cells are conditioned by particular cytokines and soluble mediators secreted by different effector and regulatory immune cell populations.Dysfunctional CD8+ T cells in patients with Chagas' disease are associated with higher parasite loads and more severe clinical disease.Several strategies, including vaccines and trypanocidal drugs with immunomodulatory properties, have shown diverse success to enhance CD8+ T cell immunity, reduce parasite burden, and limit clinical severity.