Enhanced migratory capacity of T lymphocytes in chagasic patients with more severe degree of heart disease.

PEREZ A; SILVA-BARBOSA SD; BERBERT L; REVELLI S; BELOSCAR J; BOTTASSO O; SAVINO W

Buenos Aires

Congreso; First French-Argentine Immunology Congress; 2010

SAI-Sociedad Francesa de Inmunología

It is estimated that 30% of individuals bearing Chagas disease (CD) progress to chronic myocarditis, displaying T cell-inflammatory infiltrates in heart tissue. The presence of inflammatory cytokines and the enhanced deposition of fibronectin (FN) in the myocardium may contribute to the recruitment of inflammatory T cells, resulting in the establishment of carditis. In order to further approach the dynamics of T cell migratory events in CD, we performed FN-driven migration assays with PBMCs from chronic chagasic individuals. Migrating T lymphocytes were then evaluated for the cytofluorometric profiles of molecules involved with activation and cell migration. Serologically positive for T. cruzi (S+) patients without heart involvement were classified as asymptomatic (ASY, n=15) and S+ patients with severe carditis as SEV (n=13). Healthy volunteers acted as a control group (Co, n=15). The percentage of circulating CD3+T cells was decreased in ASY and SEV compared to Co (p<0.05 in both cases), although T cell expressing HLA-DR and VLA-4 (an integrin-type FN receptor) was increased, especially in SEV (p<0.05vs Co). SEV also showed an abnormal presence of CD4+CD8+ T cells with activated phenotype in periphery (p<0.05 vs Co). In vitro capacity of T cells to migrate through FN showed an increased migratory response that correlated to the severity of heart disease (SEV vs ASY p<0.05). The SEV group presented a significantly higher migratory capacity of HLA-DR+VLA-4+ T cells when compared to ASY and Co groups (p<0.05 in both cases). Present data are compatible with the existence of disturbances in T cell migration during CD as it was previously showed in an experimental model of T. cruzi infection. Differences in terms of T cell migratory responses in SEV compared to ASY may partly explain why ASY individuals do not evolve to cardiac illness remaining for the lifetime in the latent stage. Financial support: PIP-CONICET (Argentina); Fiocruz, CNPq, Capes and Faperj (Brazil).