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.
Highlights
Expression of either CD4 or CD8 on mature peripheral CD3+ T cells is considered to be a mutually exclusive event as a result of the thymic selection, reflecting the specific functions of each major T cell subpopulation
K1 tetramer positive double positive (DP) T cell produced little IFN-c, they displayed degranulation activity that was increased in symptomatic patients
K1specific DP T cells can migrate to the heart tissue
Summary
Expression of either CD4 or CD8 on mature peripheral CD3+ T cells is considered to be a mutually exclusive event as a result of the thymic selection, reflecting the specific functions of each major T cell subpopulation Contrary to this conventional dichotomy, circulating CD4+/CD8+ double positive (DP) T cells have been identified in human peripheral blood and represents between 1 and 3% of the total T lymphocytes population [1]. Based on the intensity of CD4 and CD8 expression by flow cytometry, two subsets of DP T cells have been defined: CD4dim/ CD8bright and CD4bright/CD8dim lymphocytes [3] Previous studies of their phenotypic characteristics have shown that the majority of these cells have memory phenotype (CD45RO+). No previous studies of double positive T cells in parasite infections have been carried out
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