Are increased frequency of macrophage-like and natural killer (NK) cells, together with high levels of NKT and CD4 super(+)CD25 super(high) T cells balancing activated CD8 super(+) T cells, the key to control Chagas' disease morbidity?

• Published in: Clinical and experimental immunology 2006-07, Vol.145 (1), p.81-92
• Main Authors: Vitelli-Avelar, D M, Sathler-Avelar, R, Massara, R L, Borges, J D, Lage, P S, Lana, M, Teixeira-Carvalho, A, Dias, JCP, Eloi-Santos, S M, Martins-Filho, O A
• Format: Article
• Language: English
• Subjects: Trypanosoma cruzi
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1111/j.1365-2249.2006.03123.x

The immunological response during early human Trypanosoma cruzi infection is not completely understood, despite its role in driving the development of distinct clinical manifestations of chronic infection. Herein we report the results of a descriptive flow cytometric immunophenotyping investigation of major and minor peripheral blood leucocyte subpopulations in T. cruzi-infected children, characterizing the early stages of the indeterminate clinical form of Chagas' disease. Our results indicated significant alterations by comparison with uninfected children, including increased values of pre-natural killer (NK)-cells (CD3 super(-) CD16 super(+) CD56 super(-)), and higher values of proinflammatory monocytes (CD14 super(+) CD16 super(+) HLA-DR super(++)). The higher values of activated B lymphocytes (CD19 super(+) CD23 super(+)) contrasted with impaired T cell activation, indicated by lower values of CD4 super(+) CD38 super(+) and CD4 super(+) HLA-DR super(+) lymphocytes, a lower frequency of CD8 super(+) CD38 super(+) and CD8 super(+) HLA-DR super(+) cells; a decreased frequency of CD4 super(+) CD25 super(HIGH) regulatory T cells was also observed. These findings reinforce the hypothesis that simultaneous activation of innate and adaptive immunity mechanisms in addition to suppression of adaptive cellular immune response occur during early events of Chagas' disease. Comparative cross-sectional analysis of these immunophenotypes with those exhibited by patients with late chronic indeterminate and cardiac forms of disease suggested that a shift toward high values of macrophage-like cells extended to basal levels of proinflammatory monocytes as well as high values of mature NK cells, NKT and regulatory T cells, may account for limited tissue damage during chronic infection favouring the establishment-maintenance of a lifelong indeterminate clinical form of the disease. On the other hand, development of an adaptive cell-mediated inflammatory immunoprofile characterized by high levels of activated CD8 super(+) cells and basal levels of mature NK cells, NKT and CD4 super(+) CD25 super(HIGH) cells might lead to late chronic pathologies associated with chagasic heart disease.