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D A Harn

Publications and source records attributed to D A Harn.

At least 37 records · Page 2Linked to original sources
PubMed1999

Generation of antigen-specific cytotoxic T lymphocytes and regulation of cytokine production takes place in the absence of CD3zeta.

The TCR-associated protein CD3zeta plays a major role in regulating the state of responsiveness to peptide-MHC complexes on the surface of antigen-presenting cells. In this paper the requirement of CD3zeta in the generation of cytotoxic T cells was compared with its requirement in cytokine gene activation in two mutant mice: ZKO mice with a disrupted CD3zeta gene and ZTG mice in which a truncated CD3zeta segment was expressed as a transgene on the ZKO background. Upon infection of ZTG mice with lymphocytic choriomeningitis virus (LCMV), antigen-specific cytotoxic T lymphocyte (CTL) responses were detected, identical to responses in wild-type mice. In addition, antigen-specific CTL responses to allogeneic class I and class II MHC in ZTG animals were indistinguishable from those in wild-type animals. However, CTL responses to the same major antigens were not detectable in ZKO mice. We conclude that the signal transduction pathways leading to CTL development and cytokine production can be triggered through TCR in the absence of functional CD3zeta, provided the remainder of the TCR-CD3 complex is expressed at high levels on the cell surface. Surprisingly, IFN-gamma production in response to LCMV followed the same kinetics in ZKO, ZTG and wild-type mice. However, in vitro studies showed that cytokine production in general was abnormally regulated in T lymphocytes from ZKO mice, in contrast to ZTG T cells. Taken together, these studies support the hypothesis that development of CTL can take place in the absence of functional CD3zeta. However, CTL development requires stronger TCR-initiated signal transduction events than induction of cytokine genes.

Abatacept↗
PubMed1999

Involvement of carbohydrate on phospholipase A2, a bee-venom allergen, in in vivo antigen-specific IgE synthesis in mice.

BACKGROUND: Carbohydrates on allergens are known to be important for allergenicity. However, most findings have been made with epitope analysis. In this study, we investigated the involvement of N-glycan on phospholipase A2 (PLA2), the major allergen of honeybee venom, in in vivo synthesis of specific IgE in mice. METHODS: CBA/J and C57BL/6 mice were sensitized intranasally with either native or deglycosylated PLA2 in the absence of adjuvant. After repeated sensitization, serum Ab titers against PLA2 were determined. PLA2 was deglycosylated chemically with anhydrous trifluoromethanesulfonic acid (TFMS). RESULTS: CBA/J mice showed PLA2-specific IgE production after repeated sensitization with native PLA2. They also produced PLA2-specific IgG1 predominantly, suggesting that Th2-type Ab production was induced. When we used deglycosylated PLA2 as a competitor in ELISA for detecting PLA2-specific IgE, deglycosylated PLA2 completely inhibited the binding between native PLA2 and IgE. Deglycosylated PLA2 had the same potential for inducing specific IgE synthesis as native PLA2, since sensitization with deglycosylated PLA2 also elicited IgE production in CBA/J mice. CONCLUSIONS: These results suggest that carbohydrate on PLA2 is less important than previously thought not only as a dominant IgE epitope but also in synthesis of PLA2-specific IgE in vivo.

Allergens↗
PubMed1998

Oral administration of schistosome egg antigens and insulin B-chain generates and enhances Th2-type responses in NOD mice.

In murine Schistosoma mansoni, parenteral administration of parasite eggs or saline-soluble egg antigens (SEA), generates Th2 T-cell responses to both schistosome-specific and unrelated third-party antigens. Oral administration of insulin to NOD mice suppresses or delays the onset of diabetes by skewing the response toward CD4+ Th2 cells and TGF-beta producing cells. From these two independent sets of observations, we initiated the present study to determine if oral administration of SEA would stimulate Th2-type cytokine responses when mice were fed SEA alone or in tandem with insulin B-chain. Our results show that feeding NOD mice with either insulin B-chain or SEA alone significantly inhibits proliferation to the immunizing antigen. When cytokine profiles were examined, feeding led to a predominance of IL-10 and TGF-beta production. Furthermore, feeding SEA in combination with insulin B-chain augmented the level of IL-10 production to insulin. T-cell lines established from SEA-fed and -immunized mice secreted IL-4 and IL-10 cytokines whereas the T-cell lines from control-fed mice immunized with SEA secreted predominantly IL-2 and IFN-gamma. These results demonstrate that orally administered insulin can induce regulatory T-cells secreting IL-4, IL-10, and TGF-beta and that Th2 responses to oral insulin could be augmented in a synergistic way by feeding SEA and insulin B-chain together.

Administration, Oral↗
PubMed1998

Schistosoma mansoni: genetic restriction and cytokine profile of the CD4 + T helper cell response to dominant epitope peptide of major egg antigen Sm-p40.

Granuloma formation in schistosomiasis is mediated by MHC class II-restricted CD4 + T helper lymphocytes sensitized to egg antigens. We previously reported that C3H mice, which develop large granulomas, display strong CD4 + T helper cell responses to the major egg antigen Sm-p40. Moreover, all members of a panel of egg antigen-specific T cell hybridomas responded to the Sm-p40 antigen. Given the significance of the Sm-p40 molecule in the C3H T cell repertoire against schistosomal egg antigens, the current work was undertaken to map its immunogenic epitopes, using a library of 15 synthetic overlapping 30-mer peptides. The dominant epitope recognized by polyclonal CD4 + Th cells was located in peptide 10 (amino acids 229-258); subdominant epitopes were detected in peptides 8 (amino acids 179-208) and 12 (amino acids 279-308). The anti-Sm-p40 T cell hybridomas variously responded to any one of the same three stimulatory peptides. Furthermore, studies with various mouse strains demonstrated that a strong anti-Sm-p40 response was restricted by H-2(k). Interestingly, the cells responding to peptide 10 and to the Sm-p40 antigen only secreted IL-2 and IFN-gamma, but not IL-4 and IL-10, indicating that they are entirely of the Th-1-type, a subset with demonstrated capacity to mediate egg granuloma formation. The identification of dominant epitopes within key egg antigens offers opportunities for desensitization of the CD4 + Th cells that mediate pathology in schistosomia sis.

Animals↗
PubMed1997

B-1 cell (CD5+B220+) outgrowth in murine schistosomiasis is genetically restricted and is largely due to activation by polylactosamine sugars.

Previously, we demonstrated that lacto-N-fucopentaose III, a sugar found on egg Ags of Schistosoma mansoni, stimulated splenic B cells from parasite-infected mice to proliferate and produce IL-10 and PGE2. The major source of B cell IL-10 is the B-1 subset (CD5+B220+). Thus we examined whether levels of peritoneal exudate B-1 cells changed as a consequence of infection. In CBA/J, BALB/c, and C3H/HeJ mice, we observed significant increases in B-1 cells at 2 to 4 wk postinfection, declining to baseline by 6 to 8 wk. In contrast, the percentage of B-1 cells remained unchanged in C57BL/6 and BALB/c X.id mice after infection. B-1 cells were not observed in the spleens of infected mice; however, coincident with peritoneal B-1 cell decline, splenic CD23+B220+ cells increased from 11% to 30%. Peritoneal B-1 cells could also be expanded by injection of soluble egg Ag, but not by its deglycosylated form, suggesting a role for carbohydrates in B-1 recruitment. In addition, these cells secreted in vitro large amounts of IL-10 in response to lacto-N-fucopentaose III. Further, this sugar induced B-1 cell outgrowth in CBA/J and C3H/HeJ mice, but not in C57BL/6 mice. Thus, early activation of polylactosamine-reactive, IL-10-producing peritoneal B-1 and splenic B cells may be related to early dominance of the Th2-type CD4+ T cell subset. The degree to which this occurs may in part explain differences in the degree of granulomatous pathology reported among various strains of mouse.

Amino Sugars↗
PubMed1997

Analysis of the immune response elicited by a multiple antigen peptide (MAP) composed of two distinct protective antigens derived from the parasite Schistosoma mansoni.

In this report we analyse the immune response elicited by a Multiple Antigen Peptide (MAP), containing three peptide sequences derived from two distinct vaccine candidates against schistosomiasis; the Schistosoma mansoni 28 kDa Gluthatione-S-Transferase (Sm28GST) and the Schistosoma mansoni Triose-Phosphate-Isomerase (sTPI). We examined the immunogenicity of this construct, named MAP 'DA', in three distinct mouse strains. The B-cell response, studied by measuring the production of different IgG isotypes, was mainly directed against the peptide derived from the Sm28GST, but also against the whole Sm28GST protein. In contrast, the T-cell response, as assessed by proliferation assay and cytokine mRNA expression, was directed against the MAP construct, the peptides derived from the sTPI protein and the whole sTPI protein. Significantly, T-cells from all MAP 'DA'-immunized mice, restimulated in vitro was the sTPI antigen, expressed IFN-gamma specific messengers. This cytokine has been described to play a major role in the reduction of the Schistosoma mansoni pathology. We thus demonstrate that a single MAP construct, composed of peptides from distinct antigens of Schistosoma mansoni, induced a B- and T-cell response, including production of potentially protective IFN-gamma, irrespective of the MHC background.

Animals↗
PubMed1996

B-cell outgrowth and ligand-specific production of IL-10 correlate with Th2 dominance in certain parasitic diseases.

In many parasitic infections, dominant T helper cell (Th) type-2 CD4+ T cell responses exacerbate the disease. We have previously demonstrated that lacto-N-fucopentaose-III (LNFPIII), a sugar found on soluble egg antigens (SEA) of Schistosoma mansoni, stimulates splenic B cells from parasite-infected mice to proliferate and produce IL-10, a cytokine that promotes the generation of Th2 immune responses. In the present study, we extend our observations on ligand-specific activation of IL-10 producing B cells to leishmaniasis and lymphatic filariasis. We report here that infection with Leishmania major increases the splenic B220+ B cell subset in BALB/c mice, but not BALB/c. xid (lacking B-1 cells and carrying defective B-2 cells). In addition, these B cells secrete large amounts of IL-10 in vitro in response to stimulation with soluble leishmanial extract (LSE), LNFPIII, or SO4-Lewis(x). We also observed that injection of LSE increased the level of peritoneal exudate (PeC) B-1 cells (CD5+B220+) in BALB/c mice, but not C57BL/6, as compared to buffer-injected controls. Further, LSE elicited PeC B cells secreted IL-10 in response to LSE as well as to the sugars tested. A similar differential secretion of IL-10 by splenic B cells from BALB/c and BALB/c.xid was seen after S. mansoni infection. Likewise, injection of soluble microfilarial extract (MFX) resulted in an increase in percentage of PeC B-1 cells in BALB/c mice, but not C57BL/6, and these cells secreted IL-10 in response to stimulation with MFX or phosphorylcholine (PC). Collectively, these results suggest a correlation between expansion of ligand-specific IL-10 producing B and B-1 cells with dominance of Th2-type T cells in mice with the susceptible phenotype for these diseases.

Animals↗
PubMed1996

Association of hepatosplenic schistosomiasis with HLA-DQB1*0201.

Major histocompatibility class II alleles of 351 persons living in an area endemic for Schistosoma mansoni in northeastern Brazil were characterized at three loci (DRB1, DQA1, and DQB1). Contingency analyses were used to compare allele frequencies with high egg excretion, proliferative response to schistosome soluble egg antigens (SEA), and occurrence of severe, biopsy-confirmed hepatosplenic disease. There were no associations of HLA-DR or DQ with egg excretion. Patients positive for DRB1*01, DQA1*0101, or DQB1*0501 were less likely to respond to SEA than was the overall study population. However, using stringent Bonferroni correction (multiplying P values by the number of alleles tested; P x 35), none of these associations with SEA responsiveness remained significant. Hepatosplenic disease was less likely in patients positive for DRB1*11 and was more likely in patients positive for DRB1*07 or DQB1*0201. However, only the DQB1*0201 association remained significant (odds ratio = 3.72; P < .005) following Bonferroni correction.

Adolescent↗
PubMed1996

Interleukin-12 and -10 and gamma interferon regulate polyclonal and ligand-specific expansion of murine B-1 cells.

B-1 cells (CD5+ B220+) are a self-replenishing lineage of B cells which are autoreactive and capable of producing large amounts of interleukin-10 (IL-10). In mice experimentally infected with the human helminth parasite Schistosoma mansoni, expansion of B-1 cells is seen in the peritoneal cavity just prior to egg laying. In naive mice, B-1 cell expansion can be elicited by intraperitoneal injection of saline soluble egg antigens (SEA) or the polylactosamine sugar lacto-N-fucopentaose III (LNFPIII), which contains the Lewis-X trisaccharide. In this study, we demonstrate that LNFPIII is the major stimulus in SEA responsible for expansion of B-1 cells, since SEA-induced B-1 outgrowth is blocked by multiple injections of non-cross-linked free LNFPIII. IL-10 is an autocrine growth factor for B-1 cells, and we show that B-1 outgrowth after SEA and LNFPIII administration is inhibited by injection of anti-IL-10 antibodies. Furthermore, SEA- and LNFPIII-induced expansion of B-1 cells is inhibited by in vivo administration of recombinant murine IL-12 or recombinant gamma interferon. These data suggest that activation and expansion of IL-10-producing B-1 cells are governed via cross-regulatory cytokines.

Animals↗
PubMed1996

Regulation of schistosome egg granuloma formation: host-soluble L-selectin enters tissue-trapped eggs and binds to carbohydrate antigens on surface membranes of miracidia.

Immunogenic carbohydrate epitopes are prominent in soluble egg antigens (SEA) of Schistosoma mansoni and in vivo are released through ultramicroscopic pores in the eggshell. Previously, one immunogenic carbohydrate was identified as lacto-N-fucopentaose III (LNFPIII), which contains the biologically important trisaccharide Lewis(x) (Le(x)), a weak ligand for E-, L-, and P-selectins. Selectins are involved in various inflammatory reactions, including recruitment of granulocytes. Further, L-selectin molecules are shed from leukocyte cell surfaces upon activation. These independent observations suggest that selectins may play various roles in granuloma formation and/or regulation. We tested in situ for alterations in expression of host E-, L-, or P-selectin in murine liver tissue at various times postinfection with schistosome cercariae. We found that L-selectin was expressed on cells surrounding egg granulomas, but surprisingly we also found mouse L-selectin on the surface membranes of larval miracidia within the S. mansoni ova. In contrast, neither E- nor P-selectin was found within ova. Antibodies to human or rat L-selectin or 15 other distinct mouse leukocyte surface molecules did not bind to the miracidial surface. The anti-mouse L-selectin staining of miracidia could be inhibited by wash buffer containing sulfated carbohydrates such as sulfated Le(x), heparan sulfate, fucoidan, and carrageenan. The elution studies imply that the miracidial surface and, therefore, schistosomes express sulfated glycans. The binding of soluble L-selectin to miracidia was not restricted by the genetic background of the host, as mouse L-selectin was detected on the surface of S. mansoni miracidia in livers from BALB/C, CBA/J, C57BL/6, and outbred Swiss mice. We also detected soluble mouse L-selectin binding to Schistosoma japonicum miracidia, indicating that these observations can be generalized to all schistosome infections. On the basis of these observations we hypothesize that host-soluble L-selectin traverses through pores in the eggshell and binds to target ligands on the surface membranes of miracidia; this complex formation might ultimately impede the release of soluble antigens from the eggs. The intraovum binding of mouse L-selectin to immunogenic carbohydrate antigens is a novel role for selectins, and this model may, in part, explain the down-regulation in granulomatous pathology observed following the acute phase of the disease.

Animals↗
PubMed1996

Lacto-N-fucopentaose III (Lewis x), a target of the antibody response in mice vaccinated with irradiated cercariae of Schistosoma mansoni.

Carbohydrates on soluble egg antigens are major epitopes for the antibody responses of patients and mice infected with Schistosoma mansoni. Recently, protective sera of mice vaccinated with irradiated cercariae were shown to recognize carbohydrate epitopes on schistosomal glutathione S-transferase. The present study demonstrates that carbohydrate epitopes are major targets of sera from C57BL/6J and CBA/J mice vaccinated with 15- or 50-kilorad-irradiated cercariae of S. mansoni. Antibody titers to carbohydrate epitopes increased with the number of vaccinations and were considerably higher in C57BL/6J mice than in CBA/J mice. The specificity of this anticarbohydrate response was determined by measuring antibody binding to defined oligosaccharide residues known to be present on the parasite. A predominant target of the humoral anticarbohydrate response of vaccinated mice was lacto-N-fucopentaose III, a molecule relevant for cell trafficking. We observed no binding to its nonfucosylated homolog, lacto-N-neotetraose, or to oligosaccharides present on keyhole limpet hemocyanin. The strongest antibody response to lacto-N-fucopentaose III was observed for C57BL/6J and CBA/J mice repeatedly vaccinated with 15-kilorad-irradiated cercariae, which also achieve the highest levels of protection. Immunoglobulin M was the predominant antibody class binding to lacto-N-fucopentaose III. We conclude that in the irradiated-cercariae vaccine model, C57BL/6J and CBA/J mice produce anticarbohydrate antibodies against various stages of S. mansoni and that the oligosaccharide lacto-N-fucopentaose III is one target of this response. Lacto-N-fucopentaose III and its specific antibodies may profoundly affect host resistance and parasite homing.

Animals↗
PubMed1995

Schistosoma mansoni hexokinase: cDNA cloning and immunogenicity studies.

DNA encoding a Schistosoma mansoni hexokinase (SHEX) was amplified from cDNA by the polymerase chain reaction using opposing oligonucleotide primers designed to hybridize with two short segments of hexokinase coding sequences that are well-conserved through evolution. The resulting DNA fragment was then used as a probe to identify a full-length hexokinase cDNA clone. SHEX cDNA encodes a 50-kDa protein that is approximately 46% homologous to rat hexokinase, 40% to rat glucokinase, and 34% to yeast hexokinase A. SHEX coding DNA was expressed within Escherichia coli cells and the 50-kDa recombinant product (rSHEX) was partially purified. Mice repeatedly immunized with rSHEX produced antibodies which recognize rSHEX but this offered no significant protection against subsequent cercarial challenge. On Western blots, rSHEX is weakly recognized by antisera against rat brain hexokinase but not by sera from three strains of mice experimentally infected with S. mansoni parasites or from numerous human schistosomiasis patients. Thus, unlike other reported S. mansoni glycolytic enzymes, hexokinase appears to be poorly immunogenic during schistosome infection and of limited potential as a vaccine candidate.

Amino Acid Sequence↗
PubMed1995

The irradiated cercariae vaccine model: looking on the bright side of radiation.

Schistosomes infect between 200 and 300 million people at any one time. A major strategy to reduce the impact of schistosomiasis on human health is the development of a defined antigen vaccine. Protective immunity induced in mice by irradiated cercariae may serve as a model for the development of a vaccine. In such vaccinated mice, worm burdens resulting from challenge infection can be reduced by more than 90% compared to non-vaccinated mice. During the past three decades, the irradiated-carcariae vaccine model has been dissected in the detail in order to determine factors that may be relevant to vaccination, such as the participating immune compartments, the site and kinetics of the immune response, and the antigens recognized. In this review, Dania Richter, Donald A. Harn and Franz-Rainer Matuschka highlight the research on the vaccine model, focusing on the murine model using gamma-irradiated cercariae of Schistosoma mansoni.

Journal Article↗
PubMed1994

Oligosaccharide-specific induction of interleukin 10 production by B220+ cells from schistosome-infected mice: a mechanism for regulation of CD4+ T-cell subsets.

Defining the factors and/or mechanisms that lead to the predominance of a particular CD4+ T-cell subset (Th-1 vs. Th-2) is an area of intense investigation. In murine schistosomiasis, Th-2-type T cells become predominant after deposition of eggs. The most immunoreactive egg components are glycoproteins. Previously we identified two interesting oligosaccharides found on schistosome eggs and schistosomula. One, lacto-N-fucopentaose III (LNFP-III) contains the interesting trisaccharide Lewisx, which is a weak ligand for P-selectin and is a sugar also found on the alpha and beta chains of the integrin lymphocyte function-associated molecule 1, a ligand for intercellular adhesion molecule 1. Because of the correlation between schistosome egg glycoproteins and Th-2 dominance, the present study examined whether LNFP-III and structurally related oligosaccharides were lymphostimulatory and/or able to induce factors known to down-regulate Th-1 cells. We found that LNFP-III and related sugars did induce proliferation of splenic non-T cells, B220+,CD4-,CD8- cells (B cells) of schistosome-infected and naive mice. In contrast to proliferation, LNFP-III was the only oligosaccharide that induced spleen cells to produce large amounts of interleukin 10 and prostaglandin E2, two molecules known to down-regulate Th-1 cells. Further, only spleen cells from infected mice produced cytokines after oligosaccharide stimulation. Interestingly, LNFP-III stimulation did not induce production of interleukin 4. Thus, a specific carbohydrate ligand has been identified that stimulates B cells to proliferate and produce factors that down-regulate Th-1 T cells. Further, we suggest that identical or structurally related ligands may contribute to the known Th-1 down-regulation in other parasitic diseases and in chronic blood-vascular diseases such as human immunodeficiency virus infection and a number of metastatic carcinomas and that this effect may, therefore, be a general phenomenon.

Animals↗
PubMed1994

T and B epitope determination and analysis of multiple antigenic peptides for the Schistosoma mansoni experimental vaccine triose-phosphate isomerase.

Schistosoma mansoni triose-phosphate isomerase (TPI), a glycolytic enzyme, was originally identified as the target of the mAb M.1 that conferred protection when the antibody was administered in vivo. In this study we increase the evidence that schistosome TPI is a potential vaccine Ag by showing that it also a potent inducer of IL-2 and IFN-gamma production (Th1 responses), driving production of these cytokines in the same cell populations of infected animals that have high Th2 responses directed at other parasite egg Ag. With the goal of synthetic peptide vaccine design, rTPI was used to determine specific T and B cell epitopes recognized by two strains of mice representing high and moderate responders (C57Bl/6J and CBA/J). All selected epitopes were from nonconserved regions of TPI and thus parasite-specific. We then defined minimal size immunoreactive epitopes and synthesized four-armed multiple antigenic peptides (MAP) consisting of T and B cell epitopes that could be recognized by both strains of mice in the same molecule. Characterization of the immunoreactivity of the MAP showed that higher antibody recognition of the MAP was attained when the B cell epitope was placed on the amino termini relative to the T cell epitope, whereas equivalent immunoreactivity occurred for the T cell epitopes when located at either position. Most interesting was the finding that one of the minimal T cell epitopes, when incorporated into the MAP, required enlarging to retain immunoreactivity. Finally we showed that both the full-length TPI molecule and the final version of the MAP were immunogenic to T cells in naive animals and induced cross-recognition in the form of IL-2 and IFN-gamma production.

Amino Acid Sequence↗
PubMed1994

Heterogeneity of antigen-specific CD4+ T cell clones from a patient with Schistosomiasis mansoni.

Two subsets of differentiated murine helper T cells, Th1 and Th2, based on secretion products in response to antigen have been described (Cher & Mosmann 1987, Coffman et al. 1988, Lopez et al. 1988, Paliard et al. 1988, Patel et al. 1988, Mosmann & Coffman 1989). To analyse immunological function of antigen-specific CD4+T cells in human schistosomiasis, we produced schistosomal egg antigen-specific T cell clones from a former patient. We identified four different types of CD4+ T cell clones by analysis of cytokine production. Two of the four types of the clones corresponded to murine Th1 or Th2 subsets; a third type was of the Th0 subset (Th1 + 2) and a fourth type produced IL-5 dissociated from IL-4. Analysis of the antigen(s) recognized by these T cell clones showed that all of the clones proliferated in response to soluble egg antigen(s) (SEA) found within a pl fraction whose pH was 5.2. T cell Western blot analysis of the stimulatory pl fraction demonstrated that the apparent Mr of the relevant antigens recognized by the clones were 38 kDa for the Th2 homologue, and 45-55 kDa for the Th1 homologue.

Animals↗
PubMed1994

Soluble intercellular adhesion molecules in human schistosomiasis: correlations with disease severity and decreased responsiveness to egg antigens.

Granuloma formation, the principal pathologic consequence of infection with Schistosoma mansoni, is a complex process involving intricate cell-cell interactions in which intercellular adhesion molecules are likely to participate. To examine this possibility, sera of schistosomiasis patients in various clinical groups were assayed for the presence of soluble intercellular adhesion molecule 1 (sICAM-1) and soluble E-selectin (sE-selectin). Comparisons were made between groups with different infection intensities (as predicted by fecal egg count) as well as between groups with severe (hepatosplenic) or milder (intestinal) pathology. All groups had elevated levels of sICAM-1 compared with controls. Also, patients in the high egg-excreting and hepatosplenic groups had significantly higher levels of serum sICAM-1 than patients in the low-egg-excreting and intestinal groups, respectively. The levels of sE-selectin were significantly elevated in the sera of all patients except those in the hepatosplenic group compared with controls. Patients in the intestinal group had significantly higher levels of sE-selectin in their sera than did hepatosplenic group patients, but serum sE-selectin levels of high- and low-egg-excreting patients were comparable. A striking finding of this study was the inverse correlation observed between sICAM-1 levels and peripheral blood mononuclear cell responses to schistosome soluble egg antigens (SEA) but not with responses to other schistosome antigens, purified protein derivative, or mitogen. Because ICAM-1 can perform a costimulatory function in antigen-presenting cell-T cell interactions, it is possible that shedding of ICAM-1 in the granuloma microenvironment interrupts proper costimulation, leading to unresponsive SEA-specific T cells. In this way, sICAM-1 could be one factor contributing to the observed modulation of cellular responses to SEA in chronic human schistosomiasis.

Adolescent↗