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J Mestecky

Publications and source records attributed to J Mestecky.

At least 55 records · Page 3Linked to original sources
PubMed1998

Influenza virus-infected epithelial cells present viral antigens to antigen-specific CD8+ cytotoxic T lymphocytes.

We have investigated the mechanisms involved in the clearance of viral infection at the epithelium level by analyzing the activity of influenza virus-specific cytotoxic T lymphocytes (CTL) against virus-infected CMT-93 intestinal epithelial cells. Epithelial cells infected with live influenza virus effectively present viral antigens and were lysed by both homotypic and heterotypic influenza virus-specific CD8+ T cells. These results shed new light on the control of viral infection through the elimination of virus-infected epithelial cells by virus-specific CTL and demonstrate that CMT-93 cells furnish an appropriate model for in vitro evaluation of CTL activity against virus-infected epithelial cells.

Animals↗
PubMed1998

Mucosal immunity in the female reproductive tract: correlation of immunoglobulins, cytokines, and reproductive hormones in human cervical mucus around the time of ovulation.

Mucosal surfaces serve as the portal of entry for many viral, bacterial, and parasitic infections. Understanding the immunity at mucosal membranes is essential to enhancing protection and decreasing infections. To evaluate the humoral and cellular immunity in the female reproductive tract, 15 reproductive-age women with a history of regular, cyclic monthly menses were recruited for this study. The presence of immunoglobulins and cytokines in cervical mucus was correlated with the production of reproductive hormones in sera. Cervical mucus specimens were collected at each daily visit beginning on cycle day 8 and continuing for 5 days postovulation. Volunteers were monitored by daily urinary LH testing coupled with transvaginal ultrasonography to ascertain follicular collapse. The cervix was washed in sterile saline before aspirating the cervical mucus from the cervical canal. Collection volumes ranged between 50 and 800 microl and were considered to represent the total mucus produced. Estradiol displayed the characteristic biphasic pattern with a peak before ovulation and in the luteal phase. Both IgG (30 mg/dl) and IgA (15 mg/dl) had a biphasic pattern with peak immunoglobulin levels detected 1 day before the estradiol peak and increasing again just after ovulation. Peak interleukin 10 (40 pg/ml) levels corresponded precisely with estradiol peak levels just before ovulation. Peak interleukin 1beta (1.3 ng/ml) levels occurred approximately 1 day before the estradiol peak. No apparent pattern in interleukin 6 (150 pg/ml) could be ascertained. Our data suggest a correlation between the IgG and IgA immunoglobulin levels, interleukin 1beta and interleukin 10, in the female reproductive tract and estradiol levels in the circulation. The increase in immunoglobulins and cytokines occurs approximately 1 day before the peak estradiol production before ovulation. These data suggest a role for cytokines and hormones in the regulation of reproductive tract immunity.

Adult↗
PubMed1998

Passive and active protection against disorders of the gut.

The large surface area of mucosal surfaces, particularly of the gastrointestinal tract, is protected against microorganisms and environmental antigens by various innate factors (e.g., mucins, lactoferrin, and others) and specific antibodies which are of IgA, or in some species, IgG Isotypes. Passive protection provided by effective prenatal transplacental transport of maternal antibodies and/or post-natal consumption of milk antibodies in breastfed newborns, is essential for the survival of neonates. Passive protection of mucosal surfaces by pre-formed antibodies in non-breast juveniles or adults is currently used only on an experimental basis: IgA-enriched preparations of gamma-globulin have been successfully given to children, and antibodies specific for several gastrointestinal pathogens have been isolated from immunized cows' milk, hens' eggs, or transgenic plants. Systemic administration of pre-formed antibodies is effective for protection against intestinal pathogens in species (e.g., mice, rats) endowed with efficient hepatobiliary transport of IgA into the gut lumen. However, this route of antibody administration is of limited efficiency in other species, including humans, in which almost all intestinal antibodies are produced locally by plasma cells in the gut mucosa and are not derived to a significant degree from the circulation. Active immunization is preferable for long-lasting protection. The site of immunization and presence of lymphoid tissues with inductive potential play an essential role in generating humoral immune responses in mucosal secretions. The relative efficiency of immunization routes (e.g., oral, nasal, rectal or genital) in the induction of preferential antibody responses in the intestinal secretion has not been studied extensively. Furthermore, suitable antigen delivery systems for achieving this goal must also be considered.

Animals↗
PubMed1997

Structural differences among serum IgA proteins of chimpanzee, rhesus monkey and rat origin.

Asparagine-linked sugar chains were quantitatively released from chimpanzee, Rhesus monkey and rat IgA proteins as oligosaccharides by hydrazinolysis, converted to radioactive oligosaccharides by reduction with NaB3H4, and separated into neutral and two acidic fractions by paper electrophoresis. The acidic oligosaccharides were converted to neutral ones by sialidase digestion, indicating that they are sialyl derivatives. However, the content of N-acetyl and N-glycolyl neuraminic acids was different among three species. The neutral and sialidase-treated acidic oligosaccharides were fractionated by Bio-Gel P-4 column chromatography in combination with linkage-specific sequential exoglycosidase digestion. Although IgA molecules from these species have mainly biantennary complex-type sugar chains, the contents of fucose and bisecting N-acetylglucosamine residues displayed marked species differences. In addition to these sugar chains, a small amount of the high mannose-type sugar chains was detected in chimpanzee and rat, but not in Rhesus monkey IgA. These results indicated that the processing of asparagine-linked sugar chains of IgA is different in each species.

Animals↗
PubMed1997

Rectal immunization for induction of specific antibody in the genital tract of women.

The purpose of the current study was to examine potential routes of vaccine administration for the induction of antigen-specific responses in the genital tract of women. Sixteen women were enrolled in this study, and the level of influenza-specific antibodies induced in the genital tract was measured after rectal or intramuscular immunizations. Both methods of administration induced significant increases in the concentration of flu-specific IgA found in cervical secretions within 28 days after vaccination. Initially flu-specific IgG antibodies were not induced in the genital tract by either route. As expected both IgA and IgG flu-specific antibodies were dramatically increased in serum after intramuscular vaccination. In contrast, rectal administration did not induce significant IgA responses, and only small flu-specific IgG increases in serum. Six months after administration, IgA flu-specific antibody concentrations were significantly higher than baseline levels in vaginal secretions and saliva isolated from both subject groups and flu-specific IgG concentrations in cervical secretions were high in the rectal immunization group. The long-term presence of both IgG and IgA antibody in genital secretions suggests that rectal immunization may be an effective method for induction of immune protection in the genital tract of women.

Administration, Rectal↗
PubMed1997

Galactose-deficient IgA1 in sera of IgA nephropathy patients is present in complexes with IgG.

IgA1 proteins from sera of patients with IgA nephropathy (IgAN) are galactosylated to a lesser degree than those from healthy controls. The increased reactivity of intact or de-sialylated serum IgA1 with N-acetylgalactosamine (GalNAc)-specific lectins, Helix aspersa (HAA) and Caragana arborescens (CAA) and de-sialylated IgA1 with Helix pomatia (HPA) and Bauhinia purpurea (BPA) indicated that the Gal deficiency is in glycans located in the hinge region of IgA1 molecules. De-sialylated IgA from sera of 81 IgAN patients bound biotin-labeled lectin HAA more effectively than did de-sialylated IgA from 56 healthy controls (P < 0.0001). Similar results were observed for 67 IgAN patients and 52 controls with second lectin, CAA (P < 0.001). The binding patterns for 9 patients with mesangial proliferative glomerulonephritis of non-IgA origin were similar to those for controls. Incompletely galactosylated IgA1 capable of binding GalNAc-specific lectins was detected in complexes with IgG as demonstrated by ELISA, size-exclusion chromatography and sucrose gradient ultracentrifugation. The formation of IgA1-IgG complexes may affect the serum level of IgA1 by reducing the rate of its elimination and catabolic degradation by the liver.

Adult↗
PubMed1997

Human peritoneal B-1 cells and the influence of continuous ambulatory peritoneal dialysis on peritoneal and peripheral blood mononuclear cell (PBMC) composition and immunoglobulin levels.

In mice, peritoneal B cells are composed of a unique B-1 cell population which can repopulate the intestinal lamina propria with IgA-producing cells, as well as contribute to the majority of serum IgM. In this study, peritoneal lymphocytes from patients starting continuous ambulatory peritoneal dialysis (CAPD) and from women undergoing bilateral tubal ligation (BTL) were analysed for the presence of a B-1 cell population as well as the expression of potential homing receptors. Up to 63% of the peritoneal B cells express surface antigen CD5, and most peritoneal lymphocytes express the mucosal homing receptors, alpha4 beta7 and alphaE beta7. When analysing serial samples collected from patients from the beginning of dialysis to 1 year, no marked changes were observed in serum or salivary immunoglobulin levels, although the peritoneal lymphocyte population was reduced by 50%. These data suggest that the phenotype of human peritoneal B-1 cells is similar to that of mice, but the contributions to the immune system may differ.

Adult↗
PubMed1997

Routes of immunization and antigen delivery systems for optimal mucosal immune responses in humans.

Numerous experiments performed in humans and animals have revealed that stimulation of mucosal lymphoid inductive sites such as intestinal Peyer's patches results in parallel immune responses manifested by the appearance of S-IgA antibodies in the external secretions of remote glands. However, recent experiments suggest that inductive sites associated with the upper respiratory tract, rectum, and perhaps genital tract may also function as sources of lymphoid cells that populate, with some selectivity, certain remote mucosal effector sites. Furthermore, antigen-specific IgA antibodies can be induced in certain secretions (e.g., female genital tract) not only by immunization in the vicinity of corresponding mucosal tissues (e.g., vagina and rectum) but also by oral and especially intranasal immunization. The ineffectiveness of simple delivery of soluble antigens to mucosal membranes for immunization has stimulated extensive studies of strategies for effective delivery systems that would (a) increase the antigen absorption, (b) prevent its degradation, and (c) skew the outcome of immunization to a desired goal (protective response to infectious diseases vs. tolerance; B vs. T cell responses; mucosal vs. systemic). The induction of immune responses at a desired mucosal site can be accentuated with the use of a suitable antigen-delivery system including relevant bacterial or viral vectors, edible transgenic plants expressing microbial antigens, incorporation of antigens in biodegradable microspheres or liposomes, and linkage or coadministration of antigens with cholera toxin B subunit. However, only a few antigen-delivery systems extensively used in animal experimentation have been evaluated for their efficacy in humans. The combination of various immunization routes and the use of suitable antigen-delivery systems may accomplish an important task-the induction of mucosal immune responses at a location relevant to the site of entry of a given pathogen.

Animals↗
PubMed1996

Evaluation of monoclonal antibodies with specificity for human IgA, IgA subclasses and allotypes and secretory component. Results of an IUIS/WHO collaborative study.

51 monoclonal antibodies (McAb) with putative specificity for human IgA, the IgA subclasses, Am allotypes or secretory component (SC) were evaluated for immunoreactivity and specificity by nine laboratories employing immunodiffusion, agglutination, immunohistological assays, immunoblotting and direct binding and competitive inhibition enzyme immunoassays. McAbs specific for IgA PAN (n = 24), IgA1 (n = 7), IgA2 (n = 3), IgA2m(2) (n = 2), non-IgA2m(2) (n = 4) and SC or secretory IgA (n = 5) were identified that were immunoreactive and specific in the assays employed. The McAbs identified as IgA- or SC-reactive were shown to be non-reactive to human IgG, IgM, IgD, IgE, kappa and lambda by direct binding and competitive inhibition immunoassays. Interestingly, no McAbs with restricted specificity for IgA2m(1) were identified. Some McAbs displayed higher affinity and/or better performance in one or several of the assay groups. The IgA- and SC-specific McAbs identified in this international collaborative study have potential as immunochemical reference reagents to identify and quantitate monomeric and polymeric IgA in human serum and secretions.

Animals↗
PubMed1996

gamma/delta T cell-deficient mice have impaired mucosal immunoglobulin A responses.

Mucosal tissues of mice are enriched in T cells that express the gamma/delta T cell receptor. Since the function of these cells remains unclear, we have compared mucosal immune responses in gamma/delta T cell receptor-deficient (TCRdelta-/-) mice versus control mice of the same genetic background. The frequency of intestinal immunoglobulin (Ig) A plasma cells as well as IgA levels in serum, bile, saliva, and fecal samples were markedly reduced in TCRdelta-/- mice. The TCRdelta-/- mice produced much lower levels of IgA antibodies when immunized orally with a vaccine of tetanus toxoid plus cholera toxin as adjuvant. Conversely, the antigen-specific IgM and IgG antibody responses were comparable to orally immunized control mice. Direct assessment of the cells forming antibodies against the tetanus toxoid and cholera toxin antigens indicated that significantly lower numbers of IgA antibody-producing cells were present in the intestinal lamina propria and Peyer's patches of TCRdelta-/- mice compared with the orally immunized control mice. The selective reduction of IgA responses to ingested antigens in the absence of gamma/delta T cells suggests a specialized role for gamma/delta cells in mucosal immunity.

Animals↗
PubMed1996

The joining (J) chain is present in invertebrates that do not express immunoglobulins.

Joining (J) chain is a component of polymeric, but not monomeric, immunoglobulin (Ig) molecules and may play a role in their polymerization and transport across epithelial cells. To date, study of the J chain has been confined to vertebrates that produce Ig and in which the J chain displays a considerable degree of structural homology. The role of the J chain in Ig polymerization has been questioned and, since the J chain can be expressed in lymphoid cells that do not produce Ig, it is possible that the J chain may have other functions. To explore this possibility, we have surveyed J-chain gene, mRNA, and protein expression by using reverse transcriptase-coupled PCR, Northern blot analysis, and immunoblot analysis in invertebrate species that do not produce Ig. We report that the J-chain gene is expressed in invertebrates (Mollusca, Annelida, Arthropoda, Echinodermata, and Holothuroidea), as well as in representative vertebrates (Mammalia, Teleostei, Amphibia). Furthermore, J-chain cDNA from the earthworm has a high degree of homology (68-76%) to human, mouse, and bovine J chains. Immunohistochemical studies reveal that the J chain is localized in the mucous cells of body surfaces, intestinal epithelial cells, and macrophage-like cells of the earthworm and slug. This study suggests that the J chain is a primitive polypeptide that arose before the evolution of Ig molecules and remains highly conserved in extent invertebrates and vertebrates.

Animals↗
PubMed1996

Immunoglobulin-containing plasma cells recruited to cervical neoplasia.

OBJECTIVE: To determine the number and isotype of immunoglobulin (Ig)-containing cells that infiltrate various stages of cervical neoplasia from no lesion to invasive cancer. METHODS: By three-color immunofluorescent microscopy, the number and isotype of stromal plasma cells were determined for 91 specimens representing a spectrum of cervical epithelial neoplasia as follows: no lesion (n = 12), koilocytic atypia (n = 13), mild dysplasia (n = 21), high-grade squamous intraepithelial lesions (SIL; n = 22), and invasive carcinoma (n = 23). RESULTS: The Ig-positive cell counts were markedly increased under the low-grade SIL. Specifically, the mean number of IgG-positive plasma cells was significantly increased (P < .003) under the subepithelial stroma of mild dysplasia as compared with no SIL, high-grade SIL, or invasive carcinoma. These immunocyte infiltrates were clustered in the stroma beneath koilocytes, which also demonstrated IgG-positive intracellular staining. CONCLUSION: Low-grade cervical lesions are infiltrated by IgG plasma cells to a greater extent than high-grade or invasive cervical lesions, suggesting that antibody responses are preferentially recruited in early cervical neoplasia, giving credence to the concept that low-grade lesions represent a human papillomavirus infection of the cervix rather than a neoplastic condition.

Female↗
PubMed1996

Variations in immunoglobulins and IgA subclasses of human uterine cervical secretions around the time of ovulation.

The quantity and subclass distribution of IgA produced by the human uterine cervix may have a significant impact on the defence against sexually transmitted diseases as well as the regulation of fertility. Cervical mucus was obtained from 15 normal ovulating women around the time of ovulation. The total amounts of secreted IgA (including IgA1 and IgA2), IgG, and IgM were determined by ELISA. IgA was detected at high levels in all samples of cervical mucus. When ovulation was ascertained by daily urinary luteinizing hormone testing, IgA production was maximal 2-3 days before ovulation. Equal proportions of IgA1 and IgA2 were detected in cervical mucus, and 80% of the IgA occurred in the polymeric forms. The increased levels of IgA, the ratios of IgA1 to IgA2, and the predominance of polymeric IgA indicate that much of the IgA in human uterine cervical fluid originates from local production.

Adult↗
PubMed1996

Salivary, nasal, genital, and systemic antibody responses in monkeys immunized intranasally with a bacterial protein antigen and the Cholera toxin B subunit.

Previous attempts to induce mucosal antibodies in rhesus monkeys by enteric immunization have resulted in only modest and short-lived responses, dominated by immunoglobulin M (IgM) antibodies in the plasma. In this study, two groups of rhesus monkeys were immunized intranasally three times at 2-week intervals with a bacterial protein antigen (AgI/II) either chemically coupled to or mixed with the B subunit of cholera toxin (CT), a known potent mucosal immunogen and carrier for other immunogens. Cells secreting antibodies, predominantly of the IgA isotype, to AgI/II and to CT were detected in the peripheral blood 1 week after each immunization, indicating the dissemination of IgA-secreting precursor cells through the mucosal immune system. IgG and, to a lesser extent, IgA antibodies to both proteins were induced in the plasma commencing after the second immunization. Plasma IgE concentrations and IgE antibody levels were not consistently raised during the immunization period. IgA antibodies were found in nasal and vaginal washes. Nasal IgG but not IgA antibodies showed a significant positive correlation with plasma IgG antibody levels, suggesting that they were largely derived by transudation from the circulation. Analysis of the molecular form of vaginal IgA indicated that both secretory and monomeric forms of IgA were present in various proportions. Furthermore, neither IgG nor IgA antibodies in vaginal washes were correlated with plasma antibody responses, suggesting the contribution of locally synthesized antibodies of both isotypes. Comparison of the responses between the two groups of animals showed only sporadic significant differences, indicating that intranasal immunization with AgI/II either coupled to or mixed with the B subunit of CT was equally effective at inducing generalized IgA antibody responses in the mucosal immune system and predominantly IgG antibodies in the plasma.

Administration, Intranasal↗