T-cell repertoire analysis in acute and chronic human Chagas' disease: Differential frequencies of Vβ5 expressing T cells

Abstract

Here, we analysed the use of Vβ-TCR regions by CD4+ and CD8+ T cells from acute and chronic chagasic patients using flow cytometry. We determined the Vβ expression in cells freshly isolated from patients, as well as after in vitro stimulation with antigens derived from epimastigote (EPI) or trypomastigote (TRYPO) forms of Trypanosoma cruzi. Analysis of Vβ-TCR expression of T cells freshly isolated from patients showed a decrease in Vβ5 expression in the CD4+ T-cell population from acutely infected individuals, whereas CD4+Vβ5+ T cells were found to be increased in chronic patients with the cardiac, but not indeterminate, clinical form. After culturing peripheral blood mononuclear cells (PBMC) from chronic patients with EPI or TRYPO, we found that both antigenic preparations led to a preferential expansion of CD4+Vβ5+ T cells. EPI stimulation also led to the expansion of CD8+Vβ5+ T cells, whereas TRYPO led to the expansion of this cell population only if PBMC were from cardiac and not indeterminate patients. We observed that TRYPO stimulation led to an increase in the frequency of CD4+Vβ17+ T cells in cultures of PBMC from indeterminate patients, whereas an increase in the frequency of CD8+Vβ17+ T cells was found upon TRYPO stimulation of PBMC from cardiac patients. Despite this increase in the frequency of Vβ17+ T-cell populations upon TRYPO stimulation, the same antigenic preparation led to a much higher expansion of Vβ5+ T cells. These results show a differential expression of Vβ5-TCR in cells freshly isolated from chagasic patients in different stages of the disease and that parasite-specific antigens stimulate a portion of the T-cell repertoire with preferential usage of Vβ5-TCR.