An ultrasonographic study of liver fibrosis in patients infected with Schistosoma mansoni in north-east Brazil

Between August 1988 and July 1990, 176 patients with Schistosoma mansoni infection attending the University Hospital, Recife, Brazil received a complete clinical examination including stool examination for intestinal parasites, liver function tests, and ultrasonography. The majority were also examined by upper digestive tract endoscopy. The clinical distribution of their disease was as follows: 26.7% intestinal, 13.6% hepato-intestinal, 53.4% compensated hepatosplenic and 6.3% decompensated hepatosplenic. Infection intensity was high, with a median of 360 eggs/g of faeces. Ultrasonography showed a good correlation between the degree of hepatic periportal fibrosis and the clinical stage of disease (P < 0.0001). Of the patients with the intestinal form of schistosomiasis, 12.8% had grade I fibrosis and the others had no fibrosis; 33.3% of patients with hepatointestinal schistosomiasis had grade I fibrosis, 8.3% had grade II fibrosis, and 58.4% had no fibrosis; all the patients with hepatosplenic disease had grade II or grade III fibrosis. The degree of liver fibrosis detected by ultrasonography correlated with the degree of oesophageal varices detected by endoscopy (P = 0.0001). The degree of oesophageal varices also correlated with the presence of haemorrhage (P < 0.0001). Ultrasonography is considered superior to liver biopsy, permitting a dynamic approach to the study of schistosomiasis morbidity with precise diagnosis and simple sequential follow-up of post-treatment results.     

Frequency of schistosomiasis mansoni, of its clinicopathological forms and of the ectopic locations of the parasite in autopsies in Belo Horizonte, Brazil

The frequency of schistosomiasis mansoni, of its clinicopathological forms, and of the distribution of Schistosoma mansoni eggs in ectopic locations in each clinicopathological form were studied in 1863 complete consecutive autopsies performed in Belo Horizonte, Brazil, in the period from 1971 to 1990. Three hundred and thirteen cases of S. mansoni infection (16.8%) were found. The intestinal form was the most frequent (67.4%), followed by the hepatosplenic form without pulmonary hypertension (24.9%). The intestinal form showed a smaller number of ectopic sites and a lower percentage of involvement of these sites compared to the more severe forms, particularly the hepatosplenic form with pulmonary hypertension. The distribution of the frequency of schistosomiasis mansoni cases, of the clinicopathological forms of the disease, and of the ectopic sites of S. mansoni eggs over the decades considered showed a marked reduction in all of these parameters, particularly in the more severe forms. These findings can be explained only by earlier diagnosis of the disease and the greater efficacy of the specific chemotherapy used today, preventing progression to the more severe forms of the parasitosis.     

Lack of ultrasonographic evidence for severe hepatosplenic morbidity in schistosomiasis mansoni in Mali

The inhabitants of four villages endemic for Schistosoma mansoni in central Mali (n = 1,106 of both sexes, age range 2-80 years) and of two nonendemic villages in another part of the country were examined parasitologically and ultrasonographically to establish the prevalence of periportal liver fibrosis (PF) and other features of hepatosplenic schistosomiasis. The prevalence of S. mansoni infection ranged from 36% to 93% in the endemic villages. A severe infection (> 400 eggs/g of stool) was found in 16% of the infected individuals. No case of grade III PF (echogenic bands usually > 10 mm in diameter around the central part and major branches of the portal vein and streak-like fibrous bands that extended into the periphery of the liver) and only eight cases of grade II PF (echogenic bands usually > 10 mm in diameter around the central part and major branches of the portal vein) were found; no other signs of severe hepatosplenic disease were encountered. However, grade I PF (echogenic bands usually > 4 mm in diameter that were best visible in the area of the portal vein bifurcation and gall bladder neck) was detected in 21% of all individuals, mainly in adults. In the nonendemic villages, the prevalence of grade I PF in adults was 9%. Generally, there was no significant correlation between the grade of PF and S. mansoni egg output. In one village with a high endemicity level, however, the prevalence of grade PF I increased with the intensity of infection. Morphometric data revealed no significant influence of S. mansoni infection on portal vein stem diameter and spleen size.(ABSTRACT TRUNCATED AT 250 WORDS)     

Segmental splenectomy in schistosomiasis

Segmental splenectomy was performed in 5 patients with hepatosplenic schistosomiasis mansoni and symptomatic splenomegaly. The aim was to preserve a functional remnant comprising 20-30 per cent of the bulk of a greatly enlarged spleen. The operative technique involved devascularization of anatomic segments and suture of an omental patch to the residual spleen. This procedure was simple, well tolerated and effective in relieving abdominal discomfort and cytopenias. The residual spleens showed normal uptake of 99Tc-sulphur colloid. If long term observation confirms the value of segmental splenectomy in hepatosplenic schistosomiasis, it may become appropriate therapy for those patients with symptomatic splenomegaly who do not require portal decompression.     

Hepatitis B surface antigen carrier state in hepatosplenic schistosomiasis

The prevalence of hepatitis B surface antigen (HBsAg) was studied in 103 cases of hepatosplenic schistosomiasis (HSS), 134 control cases with a variety of illnesses including hepatointestinal schistosomiasis, and 600 blood donors, in an area endemic for both schisfosomiasis and viral hepatitis. The patients with HSS proved to be persistent carriers for HBsAg in a significantly higher proportion than the other two groups of cases. The HSS cases who were carriers of HBsAg had more clinical signs of chronic liver disease and strikingly more chronic inflammation of the portal spaces on liver biopsy. It is suggested that abnormal immunological responses in patients with HSS makes them more susceptible to become carriers of HBsAg and that the addition of this injurious factor makes their basic disease worse, and may be responsible for the development of cirrhosis in some cases.     

Epidemiologic pathology of gastric ulcer and gastric carcinoma among Japanese in Hawaii

Cell-mediated immunity in rheumatoid arthritis (RA) was assessed by skin testing with six antigens in 107 patients, 94 of whom were age, sex, and race-matched with healthy individuals or patients with diseases unrelated to immunological abnormalities. 20% of RA patients were anergic. Impaired cell-mediated immunity in the RA patients was manifested by a decrease in the magnitude of skin reactivity as well as a decrease in the incidence of positive reactions to multiple antigens. Depression in cell-mediated immunity was related to age but not to sex, duration of disease, or disease activity. A slight correlation was found between absolute peripheral lymphocyte counts and the number of positive skin tests, and was confirmed by finding an association between lymphocyte counts and the size of skin reactions. A correlation was also found between lymphocyte counts and disease activity. Four explanations of the observed depression in cell-mediated immunity in RA were considered: (1) a preoccupation of the immune mechanism of the host with cell-mediated immunity reactions related to the pathogenesis of the disease; (2) a depression of cell-mediated immune reactivity by a virus infection; (3) depression of cell-mediated immunity by therapy; and (4) immune complex suppression of cell-mediated immunity. No effect of gold therapy was found. The near universal use of salicylates or other anti-inflammatory drugs did not permit investigation of the effect of these drugs on cell-mediated immunity.     

Inhibition of lymphocyte proliferation by factor(s) produced by Schistosoma mansoni

Normal spleen cells of CBA mice or Fischer rats were cultured with mitogens or allogeneic cells, together with various substances of Schistosoma mansoni origin, and thymidine uptake was measured. The proliferation (DNA synthesis) of normal lymphocytes was inhibited by the incubation product of the parasite as well as by cell-free supernatant of schistosome culture. Inhibition was obtained only when active materials were added at the beginning of the culture. Both T and B cell proliferation were inhibited. The inhibitory activity found in cell-free supernatant suggested the release by the parasite of some factor(s) interfering with lymphocyte proliferation. Moreover, serum from rats infected by S. mansoni inhibited lymphocyte proliferation also. The inhibitor(s) appeared heat resistant, dialyzable and of low molecular weight (500-1000). Incubation of normal spleen cells with S. mansoni inhibitor(s) did not enhance the release of nonspecific suppressor cell factor. The inhibition of product(s) released by the parasite could explain part of the immunosuppression status found in schistosomiasis.     

Hepatitis-B virus and schistosomiasis infections in childhood proteinuria

Hepatitis-B surface antigen (HBsAg), circulating anti-schistosomal IgG (CSAb) and circulating specific schistosomal immune complexes (CIC) were detected, using ELISA, in sera of 40 active nephrotic children, 40 active S. mansoni infected cases and 20 apparently normal age-matched controls. The presence of HBsAg cases was significantly higher among nephrotic cases (20%), active S. mansoni cases (17.5%) than controls. Moreover, HBsAg cases were significantly higher in positive CIC S. mansoni cases than negative CIC ones. The mean O.D. readings of CSAb was significantly higher in positive HBsAg nephrotic cases than negatives. At the same time, the anti-schistosomal antibodies were higher in S. mansoni cases with proteinuria than those without. Specific CIC level was significantly higher among nephrotic and schistosomiasis cases than controls. The CIC were significantly higher in schistosomiasis cases with positive HBsAg than those with negative HBsAg and were detected in 80% of cases with proteinuria compared to 37% of cases without proteinuria with a statistically significant difference. On the other hand, CIC level was not influenced, in nephrotic cases, by the presence or absence of HBsAg. It was concluded that the presence of proteinuria was considered as a good monitor of the kidney affection either with schistosomiasis or the nephrotic syndrome or the HBsAg. The detection of CIC can be used as a good monitor too and could be included in methods of early diagnosis and/or following the disease prognosis.     

Detection of T lymphocytes and T lymphocyte subsets in lichen planus: in situ and in peripheral blood

BACKGROUND: Abnormal immune mechanisms are thought to be important in the pathogenesis of lichen planus (LP). This is a study to clarify the changes that occur in T lymphocytes and T lymphocyte subsets, both in situ and in peripheral blood. METHODS: A group of 100 patients with LP were included in this study. T lymphocytes and T lymphocyte subsets were detected in lesional skin by immunoperoxidase cell surface staining using monoclonal antibodies. Peripheral T lymphocytes and T lymphocyte subsets were also detected by indirect immunofluorescence using monoclonal antibodies. A group of 10 normal healthy subjects were used as controls. RESULTS: The study of the lesional T lymphocytes and T lymphocyte subsets demonstrated that helper T cells was the predominant subset in LP lesions in most of the patients. This predominance was evident irrespective of the duration of the disease and was more evident in late than in early lesions. The percentage of both total T lymphocytes and helper T cells in peripheral blood was decreased significantly in patients compared with controls. A significant decrease in helper T cells and the helper/cytotoxic T cell ratio was detected in patients with a longer duration of the disease. CONCLUSION: Activation of helper T lymphocytes that were found to be the predominant subsets in LP lesions may be responsible for epidermotropic cellular infiltrates leading to damage and destruction of epidermal cells.     

Pepscan mapping and fusion-related properties of the major phosphatidylserine-binding domain of the glycoprotein of viral hemorrhagic septicemia virus, a salmonid rhabdovirus

In order to define factors which are important for the development of hepatitis C virus (HCV) infection and disease in transplant patients, we examined the role of class II MHC antigen restriction in viral antigen presentation to support a hypothesis of the association of this disease with an autoimmune pathogenesis. A greater degree of histocompatibility match between these donors and their HCV-negative recipients was associated with a greater predisposition to recipient HCV liver disease (ALT elevation) posttransplant. The HCV carrier state could be identified with significant amplification of autologous mixed lymphocyte reactivity (AMLR) in both long-term hemodialysis and long-term renal transplant patients, but the AMLR was absent in end-stage liver disease patients with HCV-associated cirrhosis and was insignificantly elevated in these patients with persistent infection in the first 2 years after a new liver was transplanted. There was also a moderate reduction in autologous reactivity as well as serum HCV titers among renal transplant patients who displayed biochemical evidence of chronic liver disease as opposed to those who did not. This appeared later in the course of the disease. HCV RNA could be detected in peripheral blood mononuclear cells (PBMC) of only a portion of HCV-infected renal transplant patients and these showed significantly higher autologous reactivity. In contrast, despite the fact that observations were earlier after de novo liver transplantation, HCV RNA (i.e., earlier in the course of a new or recurrent disease process) was found in PBMC of all liver transplant recipients tested. The AMLR of noninfected laboratory volunteers could be amplified by preincubating their stimulating cells (APCs) with enriched HCV possibly in immune complex (pHCV-IC). This amplification appeared only with specific combinations of HCV strains with HLA DR serotypes. In addition, HCV-primed T cells could be generated to the virus which displayed accelerated activation kinetics. Liver infiltrating lymphocytes extracted from HCV-positive end-stage diseased livers had significantly higher proliferative and cytotoxic reactivity to autologous (HCV-infected) hepatocytes than the extracted lymphocytes responding to autologous hepatocytes from HCV-negative livers. These findings offer evidence of dynamic autoimmune mechanisms in the spectrum of progression of HCV disease and may help to predict the effect of intervention at various intervals in this progression in organ transplant recipients.     

Autoimmunity, immunodeficiency and mucosal infections: chronic intestinal inflammation as a sensitive indicator of immunoregulatory defects in response to normal luminal microflora

Despite the fact that target antigens and the genetic basis of several autoimmune diseases are now better understood, the initial events leading to a loss of tolerance towards self-components remain unknown. One of the most attractive explanations for autoimmune phenomena involves various infections as possible natural events capable of initiating the process in genetically predisposed individuals. The most accepted explanation of how infection causes autoimmunity is based on the concept of "molecular mimicry" (similarity between the epitopes of an autoantigen and the epitopes in the environmental antigen). Infectious stimuli may also participate in the development of autoimmunity by inducing an increased expression of stress proteins (hsp), chaperones and transplantation antigens, which leads to abnormal processing and presentation of self antigens. Superantigens are considered to be one of the most effective bacterial components to induce inflammatory reactions and to take part in the development and course of autoimmune mechanisms. It has long been known that defects in the host defense mechanism render the individual susceptible to infections caused by certain microorganisms. Impaired exclusion of microbial antigens can lead to chronic immunological activation which can affect the tolerance to self components. Defects in certain components of the immune system are associated with a higher risk of a development of autoimmune disease. The use of animal models for the studies of human diseases with immunological pathogenesis has provided new insights into the influence of immunoregulatory factors and the lymphocyte subsets involved in the development of disease. One of the most striking conclusion arising from work with genetically engineered immunodeficient mouse models is the existence of a high level of redundancy of the components of the immune system. However, when genes encoding molecules involved in T cell immunoregulatory functions are deleted, spontaneous chronic inflammation of the gut mucosa (similar to human inflammatory bowel disease) develops. Surprisingly, when such immunocompromised animals were placed into germfree environment, intestinal inflammation did not develop. Impairment of the mucosal immune response to the normal bacterial flora has been proposed to play a crucial role in the pathogenesis of chronic intestinal inflammation. The use of immunodeficient models colonized with defined microflora for the analysis of immune reactivity will shed light on the mode of action of different immunologically important molecules responsible for the delicate balance between luminal commensals, nonspecific and specific components of the mucosal immune system.     

Cell mediated immune response in chronic liver diseases: schistosomal, viral and neoplastic

Cell mediated immune response (CMIR) was studies in 120 patients having chronic liver diseases. Patients were divided into 6 groups, (20 each). (1) Early hepatosplenic Schistosomiasis. (EHSS), (2) Late hepatosplenic Schistosomiasis. (LHSS), (3) Hepatosplenic Schistosomiasis with hepatitis B and/or C infections, (4) Hepatitis B virus cases. (HBV), (5) Hepatitis C virus cases (HCV), (6) Hepatocellular carcinoma cases. (HCC). Twenty within normal subjects taken as controls. Laboratory investigations revealed significant esinophilia in patients of group (1), haemoglobin level was significantly reduced in patients of group (1, 2, 3, & 6), serum albumin was significantly reduced in group (2). The percentage of positivity of skin testing using purified protein derivative, ranged between 10% of patients with LHSS, HBV, HCC and HSS with HBV and/or HCV, 20% of patients with HCV and 25% of patients with EHSS. Percentage of positivity in control group was 100%. The mean diameter of delayed intradermal reaction (2.2 +/- 0.5-6.1 +/- 2.1 mms.) was significantly lower in patients than controls. The response of lymphocyte transformation test to phytohaemmagglutinin was significantly lower in patients when compared to controls. The association of HBV and/or HCV with hepatosplenomegaly was accompanied with a marked depression in cell mediated immune response. Anaemia, hypoalbuminemia and nutritional status of the patients with chronic liver diseases play a major role in the suppression of cell mediated immune response.     

Functional characterization of porcine CD4+CD8+ extrathymic T lymphocytes

The porcine immune system is unique in that the expression of CD4 and CD8 antigens defines four subpopulations of resting, extrathymic (CD1-) T lymphocytes. In addition to CD4-CD8+ and CD4+CD8- T lymphocytes, CD4-CD8- and CD4+CD8+ lymphocyte subpopulations are prominent in blood as well as in lymphoid tissues. In the present study, a functional comparison was made between CD4+CD8- and CD4+CD8+ T lymphocyte subpopulations. In a primary in vitro immune response against alloantigenic stimulator cells, both subpopulations proliferated without significant differences in their reactivity. Different results were obtained when analyzing the antigen-specific functions of the two CD4+ subpopulations in a secondary response against recall viral antigen; these experiments were performed with T lymphocytes from pseudorabies virus-immunized pigs. The proliferative response against viral antigens could be assigned to the CD4+CD8+ subpopulation, whereas the CD4+CD8- subpopulation remained nonreactive. Further analyses of the virus-specific in vitro immune response revealed a major histocompatibility complex (MHC) class II restricted helper T lymphocyte reaction involving CD4 but not CD8 molecules as restriction elements. Taken together, these results demonstrate that only the extrathymic CD4+CD8+ T lymphocyte subpopulation of swine contains MHC class II-restricted antigen-specific memory T helper cells.     

Function and expression of a human idiotypic network in Schistosomiasis japonica

The cross-reactive idiotype (Hu-SJ-CRIM) is defined by polyclonal human anti-idiotypic antibodies derived from chronically S. japonicum infected patients. The present study shows that serum levels of Hu-SJ-CRIM expressed by antibodies to S. japonicum soluble egg antigen (SEA) are associated with acute infection and hepatosplenic disease. Xenogeneic anti-idiotypic antisera (anti-Hu-SJ-CRIM) suppressed human lymphocyte blastogenesis to SEA in vitro by 47-82% (P < 0.05). These anti-idiotypic antibodies also suppressed in vitro granuloma formation induced by SEA coated heads in a dose dependent manner. This immunosuppression was antigen specific in that mitogen (PHA) or non-related antigen (PPD) induced blastogenic responses were not suppressed. Surprisingly, anti-idiotypic antibodies (anti-SJ-CRIM), which describe the mouse correlate CRIM were not suppressive in the human blastogenesis or in vitro granuloma formation assays. These data indicate a dichotomy in the function and specificity of the idiotype/anti-idiotype human and murine immune networks in S. japonicum infection. Thus, only the patient derived molecules and serology form the basis for an immunoregulatory network in Schistosomiasis japonica.     

HLA class I and II polymorphisms and trachomatous scarring in a Chlamydia trachomatis-endemic population

Immune responses to Chlamydia trachomatis contribute to protection from infection and to immunopathologic disease. To test whether subjects' HLA class I (A, B, and Cw) or class II (DRbeta1 and DQbeta1) types influence risk of trachomatous scarring from chronic infection with C trachomatis, 153 cases and pair-matched controls in Gambia were studied. No HLA type was associated with protection from scarring, indicating that protective immune responses are not limited to only one or a few HLA-restricted epitopes in C. trachomatis antigens. One class I antigen, HLA-A28, was significantly more common among cases than controls (25.8% vs. 15.9%, respectively; McNemar's odds ratio [OR], 1.88; 95% confidence interval [CI] = 1.01-3.49; P = .046). In DNA subtyping of the A28 specificity, the A*6801 allele was equally common among cases and controls, but the A*6802 allele was significantly overrepresented among cases (McNemar's OR, 3.14; 95% CI = 1.32-7.44; P = .009). This association may be due to an immunopathologic HLA-A*6802-restricted cytotoxic T lymphocyte response.     

Guided bone regeneration in the treatment of periimplantitis

Immunological abnormalities frequently observed in patients with primary biliary cirrhosis are considered to be related to the pathogenesis of this disease. We performed a prospective trial to evaluate whether immune mechanisms play a role in the effectiveness of ursodeoxycholic acid (UDCA) therapy. Fifteen female patients with primary biliary cirrhosis were followed for 1 year and were then treated with UDCA (600 mg/day) for another year. Laboratory tests, including peripheral blood lymphocyte subsets assessed by dual colour fluorescence analysis using monoclonal antibodies against respective T cell markers, were evaluated at the beginning of the study, at the start of therapy and at the end of therapy. In primary biliary cirrhosis, the proportion of cytotoxic T cells, suppressor inducer T cells and alpha beta-receptor bearing T cells were significantly lower than in healthy controls. No significant changes were observed in the proportions during the year before the therapy. These reductions, however, recovered to normal ranges after 1 year of UDCA therapy. These changes were associated with an improvement in the serum levels of aspartate aminotransferase, alkaline phosphatase, gamma-globulin and IgM. The close correlation between the improvement in the imbalance of lymphocyte subsets after the therapy and the clinical status suggests that an immunological process may play a role in the effectiveness of therapy in primary biliary cirrhosis.     

Immunological characteristics of HIV-infected children: relationship to age, CD4 counts, disease progression, and survival

We have evaluated immunologic markers of disease progression in 79 children perinatally infected with HIV. Laboratory testing included T lymphocyte subsets and lymphoproliferative responses (LPR) to mitogens (PHA, Con A, and PWM), antigens (Candida, Tetanus), and alloantigens (MLC). Patients were graded into grades I, II, and III based on results of CD4 counts, and into grades A, B, and C based on results of LPR, with grades I and grades A being normal, III and C being the lowest, and II and B falling in-between. CD4 counts, CD4/CD8 ratio, and lymphoproliferative responses were markedly decreased in a majority of children. Grade III CD4 counts were almost always associated with decreased LPR. A majority of the children with grade I CD4 numbers, however, also had abnormal lymphoproliferative responses. Results of laboratory testing were analyzed in relation to clinical disease progression and survival. The first AIDS defining illnesses (ADI), especially opportunistic infections (OI), was usually associated with Grade III/C results in immunologic assays. Survival was significantly decreased in children with grade III CD4 cell counts, and grade C LPR, and was poorest if these abnormalities developed within the first year of life. In this latter age group, if the CD4 counts fell to grade III, the risk for dying was at least five times greater than those children with higher CD4 counts (grades II and I); if the proliferative responses to PHA and MLC were in Grade C, the survival was 22 months. Severe immune defects in the first year of life in children with HIV infection, as assessed by CD4 counts and a battery of functional tests, predicted rapid disease progression.     

Altered lymphocyte antigen expressions in HIV infection: a study by quantitative flow cytometry

To identify surface antigen changes that may contribute to the immune deficiency in infection with the human immunodeficiency virus (HIV), we quantified, by double-staining flow cytometry, the number of antigens of the main peripheral blood lymphocyte subsets from 30 HIV-positive persons and compared them with those of 19 HIV-negative healthy donors. Standard microbeads with different capacities to bind mouse immunoglobulins were used to convert the mean fluorescence intensity values into numbers of antigen molecules per cell, measured as antibody binding capacity. The level of expression of different lymphocyte antigens in HIV-infected patients differs from that seen in normal blood lymphocytes. Some of these surface markers are decreased, whereas others are increased, and their expression is modulated depending on the specific cell subset considered. The expression of CD3, CD4, and CD8 on T lymphocytes is significantly decreased; moreover, CD3 is down-regulated on activated and nonactivated T lymphocytes and on CD4 and CD8 cells. In contrast, the expression of CD2 on T cells is significantly increased. Natural killer cells exhibit down-regulation of CD7, normal levels of CD8 and CD56, and overexpression of CD2. Our results also identified, for most of these antigens, quantitative differences in membrane expression according to different disease stages, as assessed by the CD4 T-cell count. Quantitative flow cytometry therefore may provide useful insights into the lymphocyte functional defects characterizing HIV infection.     

Number and distribution of T lymphocytes in the small intestinal mucosa of calves inoculated with rotavirus

An understanding of the immune response to rotavirus is needed to develop effective prophylaxis. There is evidence that cell-mediated responses may be involved and to extend these observations, rotavirus antigen and the three major T cell subsets, BoCD4+, BoCD8+, and BoWC1+ gamma/delta lymphocytes were immunostained in tissue sections from calves killed at 2, 4, 6, 8 and 10 days post inoculation and quantified by image analysis. It was established that in control calves, BoCD4+ lymphocytes were predominantly in the lamina propria, while the majority of BoCD8+ and BoWC1+ gamma/delta lymphocytes were in the epithelium. Rotavirus infection was seen throughout the small intestine with the greatest amount of viral antigen detected at 4 days post inoculation in the mid and distal small intestine. Increased numbers of all subsets were detected; small increases in intraepithelial BoCD4+ and BoWC1+ gamma/delta T lymphocytes were observed especially in the distal small intestine, while larger increases in BoCD8+ cells were detected in the epithelium and lamina propria of the proximal, mid and distal small intestine. The timing and location of these increases in T lymphocyte subsets is indicative of a specific immune response involving BoCD8+ and BoWC1+ gamma/delta T lymphocytes.     

Expression of class II, but not class I, major histocompatibility complex molecules is required for granuloma formation in infection with Schistosoma mansoni

Previous studies have suggested that granulomatous inflammation in schistosomiasis is mediated by CD4+ T helper lymphocytes sensitized to parasite egg antigens. However, CD8+ T cells have also frequently been associated with the immune response to schistosome eggs. To examine more precisely the role of CD4+ and CD8+ T cells in the pathology of the schistosomal infection, we used mice with targeted mutations in major histocompatibility complex (MHC) class II or class I molecules. These mutations lead, respectively, to the virtual absence of CD4+ and CD8+ T cells. The results clearly show that schistosome-infected MHC class II mutant mice failed to form granulomas around parasite eggs. In contrast, infected MHC class I mutant mice displayed characteristic granulomatous lesions that were comparable to those in wild-type control mice. Moreover, lymphoid cells from MHC class II mutant mice were unable to react to egg antigens with either proliferative or cytokine [interferon-gamma, interleukin (IL)-4, IL-10] responses; nor were they able to present egg antigens to specifically sensitized CD4+ T helper cells from infected syngeneic control mice. By comparison, cells from MHC class I mutant mice exercised all these functions in a manner comparable with those from wild-type controls. These observations clearly demonstrate that schistosomal egg granulomas are mediated by MHC class II-restricted CD4+ T helper cells. They also suggest that CD8+ T cells do not become sensitized to egg antigens and play little role, if any, in the pathogenesis of schistosomiasis.