title: Phenotypic and functional characteristics of CD28+ and CD28- cells from chagasic patients: distinct repertoire and cytokine expression.
abstract: 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-gamma, TNF-alpha, 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-gamma, TNF-alpha 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-alpha in cardiac and with IL-10 in indeterminate CP, suggesting that these cells might have an important regulatory role in human Chagas' disease.
authors.affiliation: Department of Morphology, Institute of Biological Science, Federal University of Minas Gerais, Brazil.
authors.forename: C A S
authors.initials: CA
authors.lastname: Menezes
authors.forename: M O C
authors.initials: MO
authors.lastname: Rocha
authors.forename: P E A
authors.initials: PE
authors.lastname: Souza
authors.forename: A C L
authors.initials: AC
authors.lastname: Chaves
authors.forename: K J
authors.initials: KJ
authors.lastname: Gollob
authors.forename: W O
authors.initials: WO
authors.lastname: Dutra
mesh_terms: D000328:Adult; D018106:CD28 Antigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D014355:Chagas Disease / Q000276:immunology*; D002908:Chronic Disease; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis; D016753:Interleukin-10 / Q000032:analysis; D015847:Interleukin-4 / Q000032:analysis; D008875:Middle Aged; D010641:Phenotype; D013601:T-Lymphocytes / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D018106:CD28 Antigens; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma