title: Inhibitory Receptor Expression on CD8+ T Cells Is Linked to Functional Responses against Trypanosoma cruzi Antigens in Chronic Chagasic Patients.
abstract: In mammals, chronic diseases resulting from infectious agents have been associated with functional T cell response deficiency, a high frequency of terminally differentiated T cells, the presence of monofunctional Ag-specific T cells, and increased expression of inhibitory receptors. Similar to other chronic diseases, the progressive loss of certain functional activities during Trypanosoma cruzi infection might result in the inability to control replication of this parasite. To examine this hypothesis, we evaluated the differentiation and cell effector function of CD8(+) T cells and characterized the expression of inhibitory receptors and the presence of the parasite in the bloodstream of chagasic patients. The results showed that patients at an advanced severe disease stage had a higher frequency of terminally differentiated CD8(+) T cells than patients at an early stage of the disease. A monofunctional CD8(+) T cell response was observed in patients at an advanced stage, whereas the coexpression of markers that perform three and four functions in response to parasite Ags was observed in patients at a less severe disease stage. The frequency of CD8(+) T cells producing granzyme B and perforin and those expressing inhibitory receptors was higher in symptomatic patients than in asymptomatic patients. Taken together, these findings suggest that during the course of Chagas disease, CD8(+) T cells undergo a gradual loss of function characterized by impaired cytokine production, the presence of advanced differentiation, and increased inhibitory receptor coexpression.
authors.affiliation: Grupo de Inmunobiología y Biología Celular, Pontificia Universidad Javeriana, 110321 Bogotá, Colombia; Laboratorio de Parasitología Molecular, Pontificia Universidad Javeriana, 110321 Bogotá, Colombia; Instituto de Parasitología y Biomedicina López Neyra, Consejo Superior de Investigaciones Científicas (IPBLN-CSIC), 18016 Granada, Spain;
authors.forename: Paola
authors.initials: P
authors.lastname: Lasso
authors.affiliation: Grupo de Inmunobiología y Biología Celular, Pontificia Universidad Javeriana, 110321 Bogotá, Colombia; Laboratorio de Parasitología Molecular, Pontificia Universidad Javeriana, 110321 Bogotá, Colombia;
authors.forename: Jose
authors.initials: J
authors.lastname: Mateus
authors.affiliation: Laboratorio de Parasitología Molecular, Pontificia Universidad Javeriana, 110321 Bogotá, Colombia;
authors.forename: Paula
authors.initials: P
authors.lastname: Pavía
authors.affiliation: Instituto de Arritmias Joseph Brugada, Fundación Clínica Abood Shaio, 111121 Bogotá, Colombia;
authors.forename: Fernando
authors.initials: F
authors.lastname: Rosas
authors.affiliation: Facultad de Medicina, Pontificia Universidad Javeriana, 110321 Bogotá, Colombia; and.
authors.forename: Nubia
authors.initials: N
authors.lastname: Roa
authors.affiliation: Instituto de Parasitología y Biomedicina López Neyra, Consejo Superior de Investigaciones Científicas (IPBLN-CSIC), 18016 Granada, Spain;
authors.forename: M Carmen
authors.initials: MC
authors.lastname: Thomas
authors.affiliation: Instituto de Parasitología y Biomedicina López Neyra, Consejo Superior de Investigaciones Científicas (IPBLN-CSIC), 18016 Granada, Spain;
authors.forename: Manuel C
authors.initials: MC
authors.lastname: López
authors.affiliation: Grupo de Ciencias Básicas Médicas, Facultad de Medicina, Universidad de los Andes, 111711 Bogotá, Colombia.
authors.forename: John M
authors.initials: JM
authors.lastname: González
authors.affiliation: Laboratorio de Parasitología Molecular, Pontificia Universidad Javeriana, 110321 Bogotá, Colombia;
authors.forename: Concepción J
authors.initials: CJ
authors.lastname: Puerta
authors.affiliation: Grupo de Inmunobiología y Biología Celular, Pontificia Universidad Javeriana, 110321 Bogotá, Colombia; acuellar@javeriana.edu.co.
authors.forename: Adriana
authors.initials: A
authors.lastname: Cuéllar
mesh_terms: D000328:Adult; D000368:Aged; D000953:Antigens, Protozoan / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002454:Cell Differentiation / Q000276:immunology; D014355:Chagas Disease / Q000276:immunology* / Q000473:pathology; D002908:Chronic Disease; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011971:Receptors, Immunologic / Q000276:immunology*; D014349:Trypanosoma cruzi / Q000276:immunology*
chemical_list: D000953:Antigens, Protozoan; D011971:Receptors, Immunologic