Presence of antigen-experienced T cells with low grade of differentiation and proliferative potential in chronic Chagas disease myocarditis.

ARGUELLO R; VIGLIANO CA; CABEZA MECKERT P; VIOTTI R; GARELLI F; FAVALORO LE; FAVALORO RR; LAGUENS RP; LAUCELLA S

PLOS NEGLECTED TROPICAL DISEASES

PUBLIC LIBRARY SCIENCE

Lugar: San Francisco; Año: 2014 vol. 8 p. 1 - 14

1935-2735

BACKGROUND: The main consequence of chronic Trypanosoma cruzi infection is the development of myocarditis in approximately 20-30% of infected individuals but not until 10-20 years after the initial infection. We have previously shown that circulating interferon-gamma-secreting T cells responsive to Trypanosoma cruzi antigens in chronic Chagas disease patients display a low grade of differentiation and the frequency of these T lymphocytes decreases along with the severity of heart disease. This study sought to explore the expression of markers of T cell differentiation, inhibitory receptors, transcription factors of type 1 or regulatory T cell profiles, as well as markers of immunosenescence and active cell cycle in cell infiltrates from patients with advanced Chagas disease myocarditis. METHODOLOGY/PRINCIPAL FINDINGS: The expression of different markers for T and B cells as well as for macrophages was evaluated by immunohistochemistry and immunofluorescence techniques in cardiac explants from patients with advanced chronic Chagas disease submitted to heart transplantation Most infiltrating cells displayed markers of antigen experienced T cells (CD3+, CD4+, CD8+, CD45RO+) with low grade of differentiation (CD27+, CD57-, CD45RA-, PD-1-). A skewed T helper1/T cytotoxic 1 profile was supported by the expression of T-bet; whereas FOXP3+ cells were scarce and located only in areas of severe myocarditis. In addition, a significant proliferative capacity of CD3+ T cells, assessed by Ki67 staining, was found. CONCLUSIONS/SIGNIFICANCE: The quality of T cell responses and immunoregulatory mechanisms might determine the pattern of the cellular response and the severity of disease in chronic Trypanosoma cruzi infection.