Immunohistochemical characterization of infiltrating cells in human chronic chagasic myocarditis: Comparison with myocardial rejection process

Abstract

Cellular subpopulations that infiltrate the heart in human chronic chagasic myocarditis were defined immunohistochemically in endomyocardial biopsy (EMB) specimens. T cells formed 96.3% of the inflammatory infiltrate, predominantly CD8+ (cytotoxic/suppressor) T cells. The mean numbers of CD8+ and CD4+ (helper) T cells in the myocarditis were compared to those present in the myocardial rejection process. Mean numbers of CD8+ T cells were similar in both groups of EMB specimens while CD4+ T cell counts, CD4+/CD8+ ratios and CD4+ antigen expression were significantly lower in the chagasic group compared to the myocardial rejection group (P < 0.002). The persistent lower number and diminished expression of CD4+ T cells suggest an immunological imbalance in patients with chronic chagasic myocarditis. A possible participation of Trypanosoma cruzi parasites in the development of such immunological abnormalities is also discussed.

Chagas disease cardiomyopathy: current concepts of an old disease

“…The inflammatory infiltrate found in heart tissue of CCC patients contains macrophages, granzyme-expressing CD8+ T cells, and CD4+ T cells (HIGUCHI et al, 1993). Data from CCC patients show that cytokine profile is shifted towards Finally, work from our group and others has brought to attention the complex role of inflammatory cytokines in CCC pathogenesis.…”

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.…”

“…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.…”

“…CD8 + T cells recognizing T. cruzi antigens, such as cruzipain and FL-160, are also found in the CCC inflammatory infiltrate (Fonseca et al 2005). Although it is difficult to locate T. cruzi nests in the myocardium of immunocompetent CCC patients, the presence of T. cruzi antigens and DNA has already been demonstrated (Higuchi et al 1993, Jones et al 1993 and an association between the persistence of parasite DNA and intense myocarditis has been reported (Benvenuti et al 2008). On the other hand, CD4 + T cells can cross-react recognizing cardiac myosin the most abundant heart protein and T. cruzi protein B13 have also been recovered from the myocardium of CCC patients (Cunha-Neto et al 1996, Abel et al 1997.…”

“…Whatever the antigenic stimulus may be, it is long-lasting and maintains the local inflammatory infiltrate. Besides the observed tissue damage, histiocytes and endothelial cells display increased expression of HLA class I and class II molecules, ICAM and E-selectin, while cardiomyocytes express increased levels of HLA class I, which are markers normally found on cells in response to local production of inflammatory cytokines (Higuchi et al 1993, Reis et al 1993a). …”