Characterization of Inflammatory Infiltrates in Chronic Chagasic Myocardial Lesions: Presence of Tumor Necrosis Factor-α+ Cells and Dominance of Granzyme A+, CD8+ Lymphocytes

Proteomic inventory of myocardial proteins from patients with chronic Chagas' cardiomyopathy

“…The local cytokine production profile is consistent with a T1-type response, with interferongamma (γ)-induced chemokines (5)(6)(7)(8)(9)(10)(11)(12). Gene expression profiling of CCC myocardial tissues showed that 15% of the known genes selectively up-regulated in CCC are IFN-γ-inducible (12).…”

“…related to the immune system, such as immunoglobulins, T cell receptor ß chain, HLA class I molecule, and granzyme A. The expression of HLA class I and granzyme A is increased expression in the myocardium from CCC patients (7,8). Granzyme A, a protein known to be produced by CD8+ cytotoxic T cells -which are highly abundant in CCC myocardium (22) -triggers apoptosis of target cells in the presence of CD8+ T cell cytotoxicity (23).…”

Viejos y nuevos conceptos en inmunidad a parásitos

“…No obstante, la presencia de estos linfocitos en el tejido cardiaco de animales, al igual que en pacientes con cardiopatía chagásica aguda y crónica, sugieren su participación en el daño del miocardio, probablemente mediante sus funciones efectoras como la producción de citocinas y la presencia de gránulos citotóxicos como perforina y fragmentinas (Reis et al, 1993, Silverio et al, 2010.…”

Immunological and non-immunological effects of cytokines and chemokines in the pathogenesis of chronic Chagas disease cardiomyopathy

“…In CCC, the inflammatory infiltrate is com-posed of macrophages (50%), B cells and T cells (10%) and very few NK cells (Milei et al 1992, Higuchi et al 1993. Also, there is a 2:1 predominance of CD8 + over CD4+ T cells, with increased numbers of granzymepositive cells (Higuchi et al 1993, Reis et al 1993b) and restricted heterogeneity of T cell receptor variable alpha chain transcripts (Cunha-Neto et al 1994), further indicating an antigen-driven inflammatory infiltrate. Several clinicopathological data suggest that the infiltrate plays a major role in the development and progression of the disease: (i) the mononuclear infiltrate is associated with local cardiomyocyte destruction and fibrosis, (ii) CCC presents a shorter survival and worse prognosis than cardiomyopathies of non-inflammatory aetiology, (iii) the frequency of myocarditis in endomyocardial biopsies correlates with the severity of the functional heart damage, being low among asymptomatic individuals with the indeterminate form, intermediate among patients with ECG abnormalities and very frequent (93%) among CCC patients with dilated cardiomyopathy (Higuchi et al 1987) and (iv) we found a positive correlation between the cellularity of the infiltrate and degree of ventricular dilation (unpublished observations) among hamsters chronically infected with T. cruzi.…”

“…Mononuclear cells infiltrating CCC heart tissue express IFN-γ, TNF-α and IL-6, with lower levels of IL-2, IL-4 and IL-10 ( Reis et al 1993b, Abel et al 2001. IL-7 and IL-15, which are cytokines that promote cell survival, expression in CCC heart tissue, is also found to be increased and may be the underlying reason for the predominance of CD8 + T cells, which express increased levels of IL-15Rα and γ c chain receptor ).…”