Characterization of memory T cells in individuals resistant to Schistosoma mansoni infection.

Schistosomiasis affects about 240 million people worldwide and is estimated that about 700 million people live in areas at risk of infection. In the context of immune response associated with infection by Schistosoma mansoni, the role of memory T cells is not well understood. AIM: To evaluate the frequency of memory CD4+ and CD8+ T cells from individuals resistant and susceptible to Schistosoma mansoni infection. METHODS AND RESULTS: We selected individuals with low (resistant) and high (susceptible) parasite burden using databases generated during previous studies carried out in the same endemic area. The cell surface markers were performed using flow cytometry. In this study, the resistant individuals showed an increase in the CD4+ memory T-cell pool associated with an increase in the central memory cell (TCM) and a decrease in the effector memory cell (TEM ). Individuals susceptible to infection had higher frequencies of effector memory cells compared to resistant individuals. CONCLUSIONS: These data suggest that resistance to S mansoni infection may be associated with an increase in the number of CD4+ memory T cells and susceptibility to infection is associated with a decrease in the central memory cell as well as high proportions of effector memory cells.

Phenotypic Characterization of CD4+ T Lymphocytes in Periportal Fibrosis Secondary to Schistosomiasis.

Schistosomiasis is a parasitic disease that affects about 166 million people around the world. It is estimated that 5%-10% of individuals with schistosomiasis develop severe forms of the disease, which are characterized by pulmonary hypertension, ascites, periportal fibrosis, and other significant complications. The chronic phase of the disease is associated with a Th2 type immune response, but evidence also suggests there are roles for Th1 and Th17 in the development of severe disease. The aim of this study was to evaluate the CD4+ T lymphocyte profile of patients with different degrees of periportal fibrosis secondary to schistosomiasis. These individuals had been treated for schistosomiasis, but since they live in a S. mansoni endemic area, they are at risk of reinfection. They were evaluated in relation to the degree of periportal fibrosis and classified into three groups: without fibrosis or with incipient fibrosis (WF/IFNE), n=12, possible periportal fibrosis/periportal fibrosis, n=13, and advanced periportal fibrosis/advanced periportal fibrosis with portal hypertension, n=4. We observed in the group without fibrosis a balance between the low expression of Th2 cytokines and high expression of T reg cells. As has already been described in the literature, we found an increase of the Th2 cytokines IL-4, IL-5, and IL-13 in the group with periportal fibrosis. In addition, this group showed higher expression of IL-17 and IL-10 but lower IL-10/IL-13 ratio than patients in the WF/IFNE group. Cells from individuals who present any level of fibrosis expressed more TGF-ß compared to the WF/IFNE group and a positive correlation with left lobe enlargement and portal vein wall thickness. There was a negative correlation between IL-17 and the thickness of the portal vein wall, but more studies are necessary in order to explore the possible protective role of this cytokine. Despite the fibrosis group having presented a higher expression of pro-fibrotic molecules compared to WF/IFNE patients, it seems there is a regulation through IL-10 and T reg cells that is able to maintain the low morbidity of this group.

Schistosoma mansoni antigens alter activation markers and cytokine profile in lymphocytes of patients with asthma.

Asthma is a chronic disease characterized by airway inflammation, obstruction and hyperresponsiveness. Severe asthma affects a small proportion of subjects but results in most of the morbidity, costs and mortality associated with the disease. Studies have suggested that Schistosoma mansoni infection reduces the severity of asthma and prevent atopy. OBJECTIVE: We evaluated the ability of S. mansoni antigens, Sm29 and Sm29TSP-2 to modulate lymphocyte activation status in response to the allergen of the mite Dermatophagoides pteronyssinus (Der p1) in cell cultures of individuals with asthma. METHODS: Thirty four patients were enrolled in this study: seventeen patients with severe asthma (SA group), seventeen patients with mild asthma (MA group) and six controls with no asthma. Peripheral blood mononuclear cells (PBMC) were obtained and stimulated with Sm29 and Sm29TSP-2 in the presence or absence of Der p1. The expression of surface markers and cytokines on lymphocytes was evaluated by flow cytometry and the levels of IL-10 in the culture supernatant were determined by ELISA. RESULTS: The addition of Sm29 and Sm29TSP-2 antigens to PBMC cultures from both groups of subjects with asthma stimulated with Der p1 reduced the frequency of CD4+CD25low cells whereas and increased frequency of CD4+CD25high population was observed compared to unstimulated cultures. Moreover, cultures stimulated with Sm29TSP-2 showed a reduction in the frequency of T cells expressing CD69, IFN-γ, TNF and TGF-ß in the MA group and an increase in the frequency of CD4+TSLPR+ T cells in the SA group. The addition of Sm29 to the cultures reduced the frequency of CD4+CD69+ and CD4+IL-5+ T cells in all asthmatic groups, and reduced the frequency of CD4+ T cells expressing IL-13 in the MA group. The cultures stimulated with Sm29 and Sm29TSP-2 showed an increase in the level of IL-10 in the supernatants. CONCLUSION: These results suggest that the addition of Sm29 and Sm29TSP-2 to the cells cultures from subjects with asthma reduced cell activation markers and altered the cytokine production pattern in a way that can potentialy control the inflammatory response associated with asthma.