The role of interleukin 10 (IL-10) and gamma interferon (IFN-␥) on the development of pathology in human Chagas' disease was investigated. Two categories of patients, low and high producers of IFN-␥, were identified based on the levels of secretion of this cytokine in the supernatant of peripheral blood mononuclear cell (PBMC) cultures. Eighty-three percent of the patients presenting with cardiac disease (CARD) of different degrees and 59% of the patients with the indeterminate form of disease (IND) were identified as high IFN-␥ producers. PBMC from IND patients classified as low IFN-␥ producers secreted significantly higher amounts of IL-10 than did those from other groups. Flow cytometry analysis demonstrated that in PBMC from the IND group, the majority of the IL-10-producing cells were monocytes (CD14 High؉ cells), whereas in the CARD group, the major sources of IFN-␥ were T lymphocytes (CD3 ؉ CD4 ؉ cells). These results suggest an association between the production of IFN-␥ by CD3؉ CD4 ؉ cells and morbidity in Chagas' disease, whereas the production of IL-10 by macrophages/monocytes leads to regulation of the immune response in IND patients. We hypothesize that an exacerbated production of IFN-␥ against Trypanosoma cruzi antigens favors the development of a strong Th1 response in CARD patients, which leads to progression of heart disease.
This review discusses the large-scale laboratory maintenance of Schistosoma mansoni. Emphasized are features which increase efficiency in such facilities, and problems most frequently encountered. Profiles are given of the long-term, high-level production of 3 strains of S. mansoni. Two of the strains, NMRI and PR-1, were of Puerto Rican origin and the other, LE, was from Brazil. Three to 8 million cercariae of each strain were usually obtained per week. The most obvious differences between the 3 strains were cercarial output per snail and snail mortality rates. Maintenance problems encountered were usually related to water quality, temperature, genetics of the parasite or snail host, predators or contaminants, feeding, or crowding of snails. Examination of the production data from these 3 life cycles led to identification of features that could be of benefit for increasing the productivity and efficiency of other S. mansoni life cycles used in research activities.
The role of cytokines on the in vitro proliferative response of peripheral blood mononuclear cells (PBMC) from Schistosoma mansoni infected patients to soluble egg (SEA) and adult worm antigens (SWAP) were evaluated. The results obtained demonstrated that the proliferative response of PBMC from chronic intestinal (INT) patients to SEA and SWAP is increased by the blockage of IL-10 with specific monoclonal antibodies (MAb). The effects of these antibodies were readily reversed by the addition of recombinant IL-10. In contrast, no effect was observed on the PBMC response of acute and hepatosplenic patients (HS) in the presence of anti-IL-10. Anti-IL-4 antibodies decreased the PBMC response of the intestinal (INT) and HS individuals to SEA and SWAP, and the PBMC response of acute patients to SEA but not to SWAP. Addition of anti-IL-5 MAb did not decrease the PBMC response of acute patients to SEA or SWAP. These results suggested that IL-10 has an important role in the modulation of the immune response in chronic asymptomatic patients and that this cytokine may be an important factor in controlling morbidity.
Volunteers living in an area where schistosomiasis mansoni is endemic were subjected to ultrasound examination and classified into groups according to the levels of fibrosis diagnosed, namely, absence of indications of fibrosis (group 0), incipient fibrosis (group 1), and moderate/severe fibrosis (group 2). Peripheral blood mononuclear cells (PBMC) collected from the volunteers were stimulated with soluble antigens from adult schistosomes or from schistosome eggs, and the production of the cytokines gamma interferon, tumor necrosis factor alpha, transforming growth factor ␤ (TGF-␤), interleukin-4 (IL-4), IL-10, and IL-13 was determined. Potential associations of the level of fibrosis with age, sex, intensity of infection, and cytokine production were investigated between the three groups. Univariate analysis identified associations of age (>50), gender (male), and absence of eggs/g of feces with moderate/severe fibrosis and an association of intensity of infection (>100 eggs) with incipient fibrosis. When cytokine production in PBMC cultures stimulated by soluble egg antigens was categorized as low or high, significant differences in the distribution of IL-13 levels were established between groups 0 and 2. No significant differences were detected between the groups in the cytokines produced by PBMC cultures stimulated with soluble antigens from adult schistosomes. When all variables were tested in multivariate analyses, only IL-13 was strongly associated with fibrosis (odds ratio ؍ 5.8; 95% confidence interval [CI] ؍ 1
A balanced host-parasite interaction during Trypanosoma cruzi infection allows for the establishment of a chronic infection that can last for many years. T cells are a major element responsible for parasite specific and non-specific immunity during the complex immune response of the host. However, the subpopulations of T cells involved in the response, as well as the exact mechanisms through which those cells are activated or rendered unresponsive, are not well defined. It is known that co-stimulatory signals, some of which are mediated via CD28, are of critical importance in the triggering of appropriate T cell responses. In this study the authors performed double-labelling studies to determine the frequency of expression of CD28 by CD4+ and CD8+ T lymphocytes in the peripheral blood of patients with Chagas' disease. The results show that chagasic patients throughout the spectrum of chronic clinical forms of the infection have significantly higher mean frequencies of CD4+CD28- and CD8+CD28-T cells, as compared with non-chagasic individuals. Considering the importance of CD28 for T-cell activation, the observed down-regulation or loss of CD28 during infection may indicate a possible basis for observed immunoregulatory events or distinct stages of T-cell activation in this infection. Recent evidence from patients with HIV/AIDS indicates that CD28- cell populations are more likely to undergo apoptosis, and increased apoptosis has been observed in experimental Chagas disease.
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