Phenotypic and functional characteristics of CD28+ and CD28− cells from chagasic patients: distinct repertoire and cytokine expression

SUMMARY Chronic human Chagas’ disease ranges from an asymptomatic to a severe cardiac clinical form. The involvement of the host's immune response in the development and maintenance of chagasic pathology has been demonstrated by several groups. We have shown that activated T‐cells lacking CD28 expression are increased in the peripheral blood of chagasic patients (CP), suggesting a relationship between these cells and disease. In order to better characterize this cell population, determining their possible role in immunoregulation of human Chagas’ disease, we evaluated the expression of TCR‐Vbeta regions 2, 3·1, 5, 8 and 17, as well as the expression of IFN‐γ, TNF‐α, IL‐4 and IL‐10 by CD28+ and CD28− cells from polarized indeterminate and cardiac CP. Flow cytometric analysis demonstrated equivalent TCR‐Vbeta usage between CD4+CD28+ and CD4+CD28− cells from all groups (chagasic and healthy controls). However, there was a predominance of Vbeta5 expression in the CD28+ and CD28− populations in the CP groups (indeterminate and cardiac). Interestingly, CD8+CD28− cells from CP, but not from nonchagasic individuals, displayed a reduced frequency of most analysed Vbetas when compared with the CD8+CD28+ subpopulation. Comparison of V‐beta expression in CD28+ or CD28− cell populations among individuals from different groups also showed several interesting differences. Functionally, cardiac CP displayed a higher frequency of IFN‐γ, TNF‐α and IL‐4 producing lymphocytes than indeterminate CP. Correlation analysis between the frequency of cytokine expressing cells, and the frequency of CD4+ T‐cells with differential expression of CD28 demonstrated that CD4+CD28− T‐cells were positively correlated with TNF‐α in cardiac and with IL‐10 in indeterminate CP, suggesting that these cells might have an important regulatory role in human Chagas’ disease.