Abstract. Cellular and humoral immune responses to Schistosoma mansoni antigen preparations were evaluated in individuals presumed to be susceptible or resistant to reinfection after chemotherapeutic cure. A consistent proliferative increase in the response to soluble egg antigen (SEA) was observed post-treatment in both the susceptible and resistant groups. However, this change was not related to resistance. Isotype studies showed that IgM antibody levels to soluble worm antigen preparation (SWAP) and cercariae antigens were significantly higher in the resistant group than in the susceptible group. Post-treatment, an increase in IgE anti-SWAP and anti-schistosomular tegument (STEG) responses and a decrease in IgG4 anti-SEA and anti-STEG responses were observed in the resistant group. These finding are similar to those we have reported previously for a putative resistant group termed endemic normals, and are compatible with immunologic studies in different endemic areas. Together, these findings indicate that even on the population level, high IgE specificities coupled with low IgG4 specificities correlate well with documented resistance to reinfection.Based on field studies following curative chemotherapy of either Schistosoma mansoni 1-3 or S. haematobium, 4,5 individuals are often categorized as being either susceptible or resistant to natural reinfection by schistosomes. These studies have shown that resistance to reinfection is an age-related phenomenon, with most people in endemic areas becoming resistant, or expressing their resistance during their second decade of life. When determined directly or by estimation, resistance appears to be unrelated to the degree of contact that the susceptible and resistant groups have with cercariaecontaining water, and is usually attributed to immunity rather than physiologic or behavioral changes with age. 4,6,7 These studies have cataloged a variety of humoral immune responses, and are in agreement with several of the correlations demonstrated between given immune responses and susceptible or resistant groups. 8,9 A number of studies have shown associations between resistance status and a balance between the level of effective anti-schistosomula antibodies and the presence of blocking antibodies. 5,[10][11][12] The latter are sometimes most easily demonstrated as antibodies to egg antigens that cross-react with epitopes present in the schistosomula tegument. 3,10The most common features that show relationships to resistance to reinfection include high levels of IgE against adult worm or larval antigens, while high levels of IgG4 and IgM antibodies against egg antigens generally parallel susceptibility. 5,9,[11][12][13][14][15] Recent studies have also reported correlations between resistance and elevated levels of IgA against a schistosome vaccine candidate (Sm 28 glutathione-S-transferase). 16,17 Further studies with other antigens have demonstrated that higher levels of IgE against a 22-kD schistosomula moiety 9 and higher levels of IgM against a 68-kD adult schistos...

Here, we analysed the use of Vb-TCR regions by CD4 and CD8 T cells from acute and chronic chagasic patients using¯ow cytometry. We determined the Vb expression in cells freshly isolated from patients, as well as after in vitro stimulation with antigens derived from epimastigote (EPI) or trypomastigote (TRYPO) forms of Trypanosoma cruzi. Analysis of Vb-TCR expression of T cells freshly isolated from patients showed a decrease in Vb5 expression in the CD4 T-cell population from acutely infected individuals, whereas CD4 Vb5 T cells were found to be increased in chronic patients with the cardiac, but not indeterminate, clinical form. After culturing peripheral blood mononuclear cells (PBMC) from chronic patients with EPI or TRYPO, we found that both antigenic preparations led to a preferential expansion of CD4 Vb5 T cells. EPI stimulation also led to the expansion of CD8 Vb5 T cells, whereas TRYPO led to the expansion of this cell population only if PBMC were from cardiac and not indeterminate patients. We observed that TRYPO stimulation led to an increase in the frequency of CD4 Vb17 T cells in cultures of PBMC from indeterminate patients, whereas an increase in the frequency of CD8 Vb17 T cells was found upon TRYPO stimulation of PBMC from cardiac patients. Despite this increase in the frequency of Vb17 T-cell populations upon TRYPO stimulation, the same antigenic preparation led to a much higher expansion of Vb5 T cells. These results show a differential expression of Vb5-TCR in cells freshly isolated from chagasic patients in different stages of the disease and that parasite-speci®c antigens stimulate a portion of the T-cell repertoire with preferential usage of Vb5-TCR.

Granuloma formation and modulation around Schistosoma mansoni eggs that are trapped in host tissues play a pivotal role during schistosomiasis. It has been demonstrated that the granuloma reactions differ in patients with the different clinical forms of the disease. The pathology during murine schistosomiasis has been correlated with a Th2 response while resistance to infection with a Th1 type response. In humans, very little is known about the role of different cytokines on the development of the disease. Here we demonstrate that IL-10 is an important cytokine regulating the in vitro granulomatous reactivity of PBMC from intestinal (INT) patients. This was evidenced by the fact that blockage of this cytokine in the in vitro granuloma assay lead to a significant increase in granuloma size with cells from INT patients but not with individuals in the acute phase or with the hepatosplenic (HS) form of schistosomiasis. These results demonstrate for the first time that, in context with the model, a Th2 cytokine in human schistosomiasis plays an important role in controlling morbidity.

We present a method for the examination of antiidiotypic cellmediated reactivity during chronic human infections. Pooled and individual sera from patients with schistosomiasis. mansoni were purified on immunoaffinity columns of schistosomal egg antigens (SEA). The eluates contained anti-SEA antibodies, but not SEA. These antibody preparations, and their F(ab')2 fragments, stimulated dose-dependent proliferation of peripheral blood mononuclear cells (PBMN) and T lymphocytes from some, but not all active or former schistosomiasis mansoni patients, and could do so autologously. Stimulation required presentation by plasticadherent cells. The eluates did not stimulate PBMN from persons who had never had schistosomiasis. Affinity-purified anti-SEA antibodies from former patients (cured for >10 yr) did not stimulate PBMN from patients with active infections. Reabsorption on SEA columns removed stimulatory activity from the eluates. We propose that multiclonal, SEA-related idiotypes expressed by some anti-SEA antibodies stimulate proliferation of T lymphocytes that express antiidiotypic specificities.

The role of serological tests on cerebrospinal fluid (CSF) in the diagnosis of neuroschistosomiasis has not been fully elucidated; the condition is essentially diagnosed on the basis of circumstantial evidence, which may lead to an erroneous diagnosis, especially in highly endemic areas. We therefore carried out a prospective case-control study in which we compared the concentrations of immunoglobulin G (IgG) specific for schistosome soluble egg antigen (SEA) present in the CSF of 54 patients with schistosomiasis mansoni myeloradiculopathy (SMMR) with those observed in a control group consisting of 41 patients with epidemiological and serological evidence of exposure to schistosomes, and with other neurological disorders that result in mild to moderate impairment of the blood-brain barrier. Anti-SEA IgG was estimated by an enzyme-linked immunosorbent assay. The sensitivity, specificity and positive and negative predictive values were 56%, 95%, 94% and 62% respectively. Likelihood ratios and the corresponding post-test probabilities were determined for 4 levels of anti-SEA IgG in CSF. A value below 0.1 micrograms/mL practically excluded the possibility of SMMR (post-test probability < 5%), a value above 1.4 micrograms/mL practically confirmed the diagnosis of SMMR (post-test probability > 96%), values of 0.1 to 0.5 microgram/mL had no diagnostic value (post-test probability approximately 45%), and values of 0.6 to 1.4 micrograms/mL were useful in some situations (post-test probability approximately 70%). We conclude that the estimation of anti-SEA IgG in the CSF is useful for the diagnosis of SMMR.