Increased CD4+/CD8+ Double-Positive T Cells in Chronic Chagasic Patients

Abstract

BackgroundCD4+/CD8+ double positive (DP) T cells have been described in healthy individuals as well as in patients with autoimmune and chronic infectious diseases. In chronic viral infections, this cell subset has effector memory phenotype and displays antigen specificity. No previous studies of double positive T cells in parasite infections have been carried out.Methodology/Principal FindingsSeventeen chronic chagasic patients (7 asymptomatic and 10 symptomatic) and 24 non-infected donors, including 12 healthy and 12 with non-chagasic cardiomyopathy donors were analyzed. Peripheral blood was stained for CD3, CD4, CD8, HLA-DR and CD38, and lymphocytes for intracellular perforin. Antigen specificity was assessed using HLA*A2 tetramers loaded with T. cruzi K1 or influenza virus epitopes. Surface expression of CD107 and intracellular IFN-γ production were determined in K1-specific DP T cells from 11 chagasic donors. Heart tissue from a chronic chagasic patient was stained for both CD8 and CD4 by immunochemistry. Chagasic patients showed higher frequencies of DP T cells (2.1%±0.9) compared with healthy (1.1%±0.5) and non-chagasic cardiomyopathy (1.2%±0.4) donors. DP T cells from Chagasic patients also expressed more HLA-DR, CD38 and perforin and had higher frequencies of T. cruzi K1-specific cells. IFN-γ production in K1-specific cells was higher in asymptomatic patients after polyclonal stimulation, while these cells tended to degranulate more in symptomatic donors. Immunochemistry revealed that double positive T cells infiltrate the cardiac tissue of a chagasic donor.ConclusionsChagasic patients have higher percentages of circulating double positive T cells expressing activation markers, potential effector molecules and greater class I antigenic specificity against T. cruzi. Although K1 tetramer positive DP T cell produced little IFN-γ, they displayed degranulation activity that was increased in symptomatic patients. Moreover, K1-specific DP T cells can migrate to the heart tissue.

Inhibitory Receptor Expression on CD8+ T Cells Is Linked to Functional Responses against Trypanosoma cruzi Antigens in Chronic Chagasic Patients

“…We observed that asymptomatic patients have a higher frequency of polyfunctional parasite-specific CD8 + T cells, which could lead to more effective parasite control, whereas the monofunctional cytotoxic parasitespecific CD8 + T cells predominant in symptomatic patients could result in tissue damage. This result correlates with that presented earlier, wherein it was shown that IFN-g production by parasitespecific cells was higher in asymptomatic patients, whereas these cells tended to degranulate more in symptomatic donors (84). In addition, in a previous study, we showed that the functional alterations in CD8 + T cells during Chagas disease are Ag specific (85).…”

IL‐9 promotes the survival and function of human melanoma‐infiltrating CD4+CD8+ double‐positive T cells

“…Of interest, numerous studies reported the presence of DP T cells with, in most cases, an increased frequency in the blood and/or in the target organ of several pathological conditions (for review see [9]), such as autoimmune diseases [10][11][12], inflammation disorders [13,14], allergies [15,16], infectious diseases [17][18][19], and cancer, postulating their involvement in pathologic events [20][21][22][23]. In these contexts, diverse functions of DP T cells were observed from cytotoxic activity [22,24] to regulatory properties [25], as well as helper potential [10].…”

La respuesta inmunitaria adaptativa en la infección crónica por Trypanosoma cruzi

“…En estos trabajos, los pacientes se clasificaron en las cuatro categorías (A-D) establecidas por la American Heart Association (AHA) (Bern, et al, 2007). Para fines prácticos, y con el objetivo de comparar los resultados, los individuos en los grupos A y B de dicha clasificación se consideraron asintomáticos (indeterminados), y los de los grupos C y D, como sintomáticos (determinados) (Giraldo, et al, 2011). La mayoría de los estudios sobre inmunidad celular en estos individuos se hacen en sangre periférica y en tejido cardiaco, y los resultados se obtienen sobre todo mediante citometría de flujo e inmunohistoquímica, respectivamente.…”

“…Entre 3 y 5 % de las células doblemente positivas se unió al tetrámero en individuos asintomáticos y sintomáticos, respectivamente. Cerca de 10 % de ellas expresaron perforina intracelular, acompañada de marcadores de degranulación (CD107), así como un nivel muy bajo de secreción de IFN-γ (Giraldo, et al, 2011). Estos resultados indican que los linfocitos doblemente positivos presentaron especificidad antigénica y capacidad citotóxica frente a los antígenos parasitarios.…”

“…Anticuerpos con miocardiopatía chagásica, y no se observaron en tejidos cardiacos derivados del trasplante en pacientes con cardiopatía crónica no chagásica (Giraldo, et al, 2011(Giraldo, et al, & 2013. Dichos resultados sugieren que la alteración en la respuesta de los linfocitos T puede estar mediada por la persistencia del antígeno parasitario en los individuos infectados, lo cual altera la activación celular y contribuye a la patogenia en la enfermedad crónica (Figura 2).…”