T-cell repertoire analysis in acute and chronic human Chagas' disease: Differentail frequencies of V beta 5 expressing T cells

Here, we analysed the use of V beta-TCR regions by CD4(+) and CD8(+) T cell s from acute and chronic chagasic patients using flow cytometry. We determi ned the V beta 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 V beta-T CR expression of T cells freshly isolated from patients showed a decrease i n V beta 5 expression in the CD4(+) T-cell population from acutely infected individuals, whereas CD4(+)V beta 5(+) 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 pat ients with EPI or TRYPO, we found that both antigenic preparations led to a preferential expansion of CD4(+)V beta 5(+) T cells. EPI stimulation also led to the expansion of CD8(+)V beta 5(+) T cells, whereas TRYPO led to the expansion of this cell population only if PBMC were from cardiac and not i ndeterminate patients. We observed that TRYPO stimulation led to an increas e in the frequency of CD4(+)V beta 17(+) T cells in cultures of PBMC from i ndeterminate patients, whereas an increase in the frequency of CD8(+)V beta 17(+) T cells was found upon TRYPO stimulation of PBMC from cardiac patien ts. Despite this increase in the frequency of V beta 17(+) T-cell populatio ns upon TRYPO stimulation, the same antigenic preparation led to a much hig her expansion of V beta 5(+) T cells. These results show a differential exp ression of V beta 5-TCR in cells freshly isolated from chagasic patients in different stages of the disease and that parasite-specific antigens stimul ate a portion of the T-cell repertoire with preferential usage of V beta 5- TCR.