Evento
Expression and functionality of co-inhibitory receptors TIGIT, TIM-3 and LAG-3 in CD4+ T cells from patients with chronic Chagas disease
Ferragut, Fatima Eneida del Valle
; Alcaráz, Paula B.; Chadi, Raul; Fernandez, Marisa; Hernandez Vasquez, Yolanda Maria; Gomez, Karina Andrea
; Acevedo, Gonzalo Raúl
Tipo del evento:
Reunión
Nombre del evento:
XXXVI Meeting of the Brazilian Society of Protozoology; XLVII Annual Meeting on Basic Research in Chagas’ Disease
Fecha del evento:
30/08/2021
Institución Organizadora:
Sociedade Brasileira de Protozoologia;
Título del Libro:
Proceedings XXXVI Meeting of the Brazilian Society of Protozoology - XLVII Annual Meeting on Basic Research in Chagas’ Disease
Editorial:
Sociedade Brasileira de Protozoologia
Idioma:
Inglés
Clasificación temática:
Resumen
Chagas disease, caused by Trypanosoma cruzi, affects 7 million people worldwide, mainly in Latin America where it is endemic. Unless treated early after infection, the disease progresses to a chronic form in which some patients develop cardiac or digestive alterations, while others stay asymptomatic. CD4+ T cell response plays critical and diverse roles during infection, and becomes impaired over time with defective cytokine release. This process known as T cell exhaustion is also defined by the upregulation of inhibitory receptors, mainly PD-1 and CTLA-4. In this work, we aimed to explore the expression of the second line of inhibitory receptors TIGIT, TIM-3 and LAG-3 in parasite stimulated CD4 T cells from patients with different stages of chronic Chagas disease (CCD), and whether their blockade restores cell functionality. Antigen-specific CD4 T cells were identified by activation induced markers (AIM) assay, using the surface molecules Ox40 and CD25. CCD patients, independently of their clinical stage, showed an increased frequency of CD4+TIGIT+ T cells. TIM-3+ CD4+ T cells were more abundant in patients with cardiac manifestations, while LAG-3+ cells were increased in asymptomatic CCD patients, with higher frequency within the non-activated cells subpopulation upon T. cruzi lysate stimulation. Preliminary data showed that TIM-3 blockade tended to increase IFN-g+ CD4+ T cells in CCD patients with cardiomyopathy. Furthermore, in the same group of subjects, the incubation with anti-TIGIT blocking antibody led to a greater frequency of IL-10+ CD4+ T cells compared to the isotype control antibody. Our results highlight the role of the inhibitory receptors TIGIT, TIM-3 and LAG-3 in the modulation of anti-T. cruzi CD4+ T cell responses, in relation with the progression of chronic Chagas disease, and paves the way for the development of novel therapeutic strategies.
Palabras clave:
TRYPANOSOMA CRUZI
,
INHIBITORY RECEPTORS
,
T CELLS
,
CHAGAS DISEASE
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Eventos(INGEBI)
Eventos de INST.DE INVEST.EN ING.GENETICA Y BIOL.MOLECULAR "DR. HECTOR N TORRES"
Eventos de INST.DE INVEST.EN ING.GENETICA Y BIOL.MOLECULAR "DR. HECTOR N TORRES"
Citación
Expression and functionality of co-inhibitory receptors TIGIT, TIM-3 and LAG-3 in CD4+ T cells from patients with chronic Chagas disease; XXXVI Meeting of the Brazilian Society of Protozoology; XLVII Annual Meeting on Basic Research in Chagas’ Disease; Sao Paulo; Brasil; 2021; 34-34
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