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Biomedical subjects

M Zeitz

Publications and source records attributed to M Zeitz.

At least 199 records · Page 11Linked to original sources
PubMed1990

Tight junction regulation during impaired ion transport in blind loops of rat jejunum.

Epithelial cell tight junction structure in self-filling blind loops of rat jejunum, a model for blind loop syndrome in humans, was analyzed morphometrically along the crypt-villus axis. In control jejunum, the number of strands and junctional depth, including meshwork depth, decreased from crypt to villus tip. In the blind loop, aberrant strands appeared below the meshwork, particularly in crypt cells. Consequently, total junctional depth was greater than in controls. Furthermore, strand number and junctional meshwork depth were increased in blind loops at the villus tip. It is that site along the crypt-villus axis which showed the most shallow junction in control jejunum. This structural change is paralleled by a three-fold increase in epithelial resistance as previously measured by alternating current impedance analysis. Relative Na over Cl permeability (PNa:Cl) was obtained from dilution potential measurements. PNa:Cl was 1.50:1 in control jejunum and 1.35:1 in the blind loop (n.s.). Considering the cation selectivity of the tight junction, the increase in epithelial resistance in blind loops cannot be attributed to a collapse of the lateral intercellular space but is due to changes in tight junctional permeability resulting from structural alteration. The blind loop syndrome represents a further example of diminished epithelial ion transport and concomitant decrease in tight junction permeability, thus supporting the general concept of regulation of the tight junction in response to active transport activity.

Animals↗
PubMed1990

gamma delta T cells in the human intestine express surface markers of activation and are preferentially located in the epithelium.

We have investigated the expression of the alpha beta and the gamma delta T cell receptor (TCR) in the human intestine. By immunohistology we found that 39% of CD3+ intraepithelial lymphocytes (IEL) expressed the gamma delta TCR compared to 3% of CD3+ lamina propria lymphocytes (LPL). Cytofluorometric analysis of isolated cells revealed a significantly higher proportion of gamma delta T cells among CD3+ IEL compared to LPL and peripheral blood lymphocytes. This was due to an increase in both CD8+ (low density) and CD4-CD8- gamma delta T cells in IEL. Most alpha beta IEL expressed high-density CD8. About 30% of both IEL and LPL expressed CD25 (alpha-chain of the IL-2 receptor). HML-1 expression was detected on nearly all IEL and on 27% of LPL. CD25 and HML-1 were preferentially expressed on intestinal alpha beta and gamma delta T cells, respectively. Thus, human gamma delta T cells are located preferentially in the gut epithelium and are phenotypically different from alpha beta T cells, which constitute the majority of both LPL and IEL.

Adult↗
PubMed1990

Special functional features of T-lymphocyte subpopulations in the effector compartment of the intestinal mucosa and their relation to mucosal transformation.

Recent studies indicate that intestinal lamina propria T cells are highly specialized lymphocytes, which differ from T cells in other compartments of the immune system in several respects. In the present study phenotypic and functional characteristics of lamina propria T cells and their possible relation to mucosal growth will be discussed. Lymphocytes from human and nonhuman primate intestine were isolated by an enzymatic procedure. Lymphocytes were studied using dual-color immunofluorescence (FACS) and functional in vitro assays. CD4 positive (helper-) lamina propria T-cells lack the CD45RA antigen and express the CD45RO antigen. This phenotype is characteristic for memory T cells. In addition intestinal T cells express IL-2 receptors and IL-2 receptor mRNA, and are able to synthesize high amounts of IL-2. Functional studies in nonhuman primates infected rectally with Chlamydia trachomatis have shown that lamina propria T cells do not proliferate after stimulation with antigen but rather provide helper function for immunoglobulin synthesis. The intestinal lamina propria therefore contains highly specialized T cells which have the phenotype of memory T cells and which are activated. Functionally these T cells can be characterized as differentiated effector lymphocytes. Recent studies from other laboratories have shown that the pattern of lymphokines produced by lamina propria T cells and the responsiveness to certain lymphokines also differ from those of other lymphocyte populations. Since T-cell-derived lymphokines are also important regulators for epithelial growth and differentiation as well as for connective tissue metabolism, lamina propria T cells might be of major importance in mucosal growth and transformation.

Animals↗
PubMed1990

Mucosal atrophy is associated with loss of activated T cells in the duodenal mucosa of human immunodeficiency virus (HIV)-infected patients.

Gastrointestinal symptoms and malabsorption are frequent in HIV-infected patients even in the absence of opportunistic infections. In earlier studies we found indications that the gastrointestinal mucosa itself may be affected by HIV. Since there is evidence that the mucosal structure is influenced by changes in the gut-associated lymphoid tissue, we have investigated mucosal structure and immune cells in HIV-infected patients. Sixty patients (3 f, 57 m; age 21-61, median 37 years; 11 at CDC stage II or III, 49 at stage IV) with gastrointestinal complaints undergoing upper endoscopy were examined for enteric pathogens. Duodenal biopsies were labelled by immunohistology for HIV antigen p24 and for lymphocyte surface markers; mucosal architecture was studied by three-dimensional morphometry. Biopsies from HIV seronegative patients without abnormal findings served as controls. In 29 patients an enteric pathogen was identified. In 22 patients HIV-infected mononuclear cells were detected in the lamina propria. In the lamina propria CD25+ cells were decreased, CD3+ and CD8+ cells were increased in HIV-infected patients compared with controls, while the numbers of CD4+, Leu8+, and HML-1+ cells, and of macrophages were not different. Patients at stage IV had decreased numbers of CD4+ T cells compared with patients at stage II or III. Villus surface area was reduced in HIV-infected patients compared with controls. Crypt depth was increased in patients with intestinal infection compared with controls while numbers of mitotic figures were normal. Patients without intestinal infection and patients with mucosal HIV-infected cells had decreased numbers of mitotic figures and normal crypt depth compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1990

The effect of an anthraquinone laxative on colonic nerve tissue: a controlled trial in constipated women.

Anthraquinone containing laxatives have been accused to cause degenerative changes in the colonic nerve tissue; prospective studies, however, are not available. This article reports the result of a semiprolective study in 11 matched pairs of chronically constipated women. Each pair consisted of one women having regularly taken an anthraquinone containing laxative for at least one year and a control person without such a medication. Six endoscopic biopsies were taken from the left colon and rectum which were evaluated by electron microscopy and subsequent ultramorphometry for the ratio of damaged to intact neurons, density of neurosecretory vesicles, axonal diameter and number of lysosomes. Medians of the three colonic locations were calculated in each individual and for each variable, and they were compared by non-parametric statistics. Medians of the ratio of damaged to intact neurons in anthraquinone treated women and controls were 0.162 and 0.146 (p = 0.0326, one-tail), medians of the number of type I vesicles were 293 and 348.5 per 100 microns 2 (p = 0.0365, one-tail), respectively. None of the other variables were different between groups. These data do not support the hypothesis that anthraquinone containing laxatives are able to provoke relevant degenerative changes in the colonic nerve tissue since the variables are either similar in both groups or only slight differences could be found which are unlikely to be of pathophysiological relevance.

Adult↗
PubMed1989

Small intestinal structure and function in patients infected with human immunodeficiency virus (HIV): evidence for HIV-induced enteropathy.

STUDY OBJECTIVE: To determine small intestinal mucosal structure and function in patients with human immunodeficiency virus (HIV) infection. DESIGN: Prospective, consecutive sample study. SETTING: Referral-based medical clinics at a municipal and a university medical center. PATIENTS: Forty-five HIV-infected patients (44 men, 1 woman) with gastrointestinal complaints. INTERVENTIONS: All patients had esophagogastroduodenoscopy. Distal duodenal biopsy samples were examined morphometrically and by quantitative enzyme histochemical techniques. Immunohistologic studies were done to determine whether HIV antigen p24 was present. Biopsy and stool samples were examined for enteric pathogens and patients were evaluated for malabsorption. MEASUREMENTS AND MAIN RESULTS: Malabsorption was common in HIV-infected patients. In 15 of 38 patients mononuclear cells infected with HIV were found in the mucosa. In 15 of 25 patients there was no detectable lactase (beta-glucosidase) activity in the duodenal brush border; when measurable, lactase (beta-glucosidase) activity was decreased (P less than 0.02). Alkaline phosphatase activity was normal. Crypt depth was greater (P less than 0.05), villous surface area was slightly smaller, and mitotic figures per crypt were not different in HIV-infected patients compared with controls. Patients without additional intestinal infection had a reduced number of mitotic figures per crypt (P less than 0.05) and normal crypt depth. The reduction in mitotic figures was most pronounced in patients with mucosal HIV antigen p24. CONCLUSIONS: The HIV-infected patients with gastrointestinal symptoms show low-grade small bowel atrophy and a maturational defect in enterocytes, which may be caused exclusively by HIV. An additional intestinal infection can mask this mucosal atrophy.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Oral administration of cyclosporin does not prevent expansion of antigen-specific, gut-associated, and spleen lymphocyte populations during Chlamydia trachomatis proctitis in nonhuman primates.

To study the effects of oral cyclosporin (CsA) administration on immune responses in the gastrointestinal tract, humoral and cellular immune responses were studied in CsA-treated nonhuman primates having Chlamydia trachomatis proctitis (lymphogranuloma venereum, LGV). There was no apparent effect of CsA treatment on the gross or microscopic appearance of LGV proctitis, but CsA-treated animals, with or without LGV infection, had lymphoid hyperplasia of spleen and mesenteric lymph nodes. CsA treatment inhibited the primary antibody response to LGV, inhibited peripheral blood lymphocyte mitogen-induced proliferation and IL-2 production, and inhibited LGV-specific proliferation of peripheral blood lymphocytes. In contrast, mitogen-stimulated proliferation of spleen, mesenteric lymph node, and lamina propria lymphocytes was not significantly inhibited in CsA-treated animals. In addition, LGV-specific proliferation of spleen and mesenteric lymph node lymphocytes was not inhibited. High mitogen-stimulated IL-2 production of lamina propria lymphocytes was only partially inhibited in CsA-treated animals. In vitro CsA treatment had the expected inhibitory effects on mitogen- and antigen-induced proliferation of spleen and mesenteric lymph node lymphocytes. Thus, although oral cyclosporin inhibits the antibody and proliferative responses of peripheral blood lymphocytes to antigens and mitogens in animals having Chlamydia trachomatis proctitis, it does not prevent the expansion of antigen-specific, gut-associated, and spleen lymphocyte populations.

Administration, Oral↗
PubMed1988

Identification of a T cell lymphoma category derived from intestinal-mucosa-associated T cells.

2 cases of precursor T cell lymphoma and 37 cases of peripheral T cell lymphoma were investigated for their reactivity with the monoclonal antibody (mAb) HML-1, which recognises human intestinal T lymphocytes but not lymph-node T cells. In all but one of the lymphomas studied, the tumour cells were unreactive with the mAb HML-1. The HML-1+ lymphoma was the only tumour that was primarily localised in the epithelium and lamina propria of the small intestine, and was associated with ulcerative jejunitis and coeliac disease. This result suggests that the HML-1+ lymphoma was derived from intestinal mucosa T lymphocytes and differs from precursor T cell lymphoblastic lymphomas and nodal and cutaneous peripheral T cell lymphomas.

Aged↗
PubMed1988

CD4 positive Leu-8 negative helper-inducer T cells predominate in the human intestinal lamina propria.

The regulatory function of peripheral blood CD4 T cells correlates with the presence or absence of the membrane glycoprotein recognized by anti-Leu-8 antibody; CD4,Leu8- T cells help Ig synthesis and CD4,Leu-8+ T cells suppress Ig synthesis. In contrast to CD4 T cells from the peripheral blood and organized gut-associated lymphoid tissues, intestinal lamina propria CD4 T cells were found to have diminished expression of the Leu-8 Ag. Therefore, studies were performed to determine whether the decreased expression of the Leu-8 Ag on lamina propria CD4 T cells correlates with a difference in the ability of peripheral blood and lamina propria CD4 T cells to regulate PWM-stimulated Ig synthesis. At high T cell to non-T cell ratios, the helper function of lamina propria CD4 T cells was significantly higher than that of peripheral blood CD4 T cells. When CD4 T cells were incubated with anti-Leu-8 antibody, the suppressor function of peripheral blood CD4 T cells was increased, but lamina propria CD4 T cells did not suppress Ig synthesis. No difference was found between the helper function of CD4,Leu-8- T cells and the suppressor function of CD4, Leu-8+ T cells isolated from either the peripheral blood or the lamina propria. Thus, the difference in the regulatory function of CD4 T cells from the peripheral blood and the lamina propria is due to the quantitative difference in CD4,Leu-8+ T cells in these sites. Consequently, the intestinal lamina propria is a site enriched in CD4,Leu-8- T cells which predominantly mediate help for Ig synthesis.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1988

Lymphocytes isolated from the intestinal lamina propria of normal nonhuman primates have increased expression of genes associated with T-cell activation.

Synthesis of interleukin-2 (IL-2) and expression of interleukin-2 receptors play central roles in T-cell activation, proliferation, and differentiation. The state of activation of T lymphocytes in the intestinal lamina propria was compared with that of circulating lymphocytes and lymphocytes isolated from the spleen or mesenteric lymph nodes of normal nonhuman primates. Lamina propria lymphocytes (LPL) had significantly higher proliferation in response to recombinant IL-2 compared with the other populations. In agreement with this finding, LPL had a significantly higher percentage of interleukin-2 receptor-positive (IL-2R+) cells as determined by staining with fluoresceinated monoclonal anti-IL-2R antibody. Two-color immunofluorescence staining showed that both CD4+ and CD8+ lamina propria T cells were IL-2R+. It was also found that the percentage of major histocompatibility complex class II-positive T cells was higher in the lamina propria. Northern blot analysis with a cDNA specific for the IL-2R showed that unstimulated LPL had easily detectable IL-2R mRNA, whereas no IL-2R mRNA was found in unstimulated lymphocyte populations from other sites. The activation of the IL-2R gene in LPL was not associated with the activation of other cellular genes (actin, major histocompatibility complex class I). Although no IL-2 bioactivity was measured in culture supernatants of unstimulated lymphocytes, concanavalin A-stimulated LPL produced significantly more IL-2 than other lymphocytes. This finding was confirmed at the molecular level as IL-2 mRNA was not detected in unstimulated LPL but was found in concanavalin A-stimulated LPL. Thus, normal lamina propria T lymphocytes have selective expression of genes associated with cell activation.

Animals↗
PubMed1988

Mucosal T cells provide helper function but do not proliferate when stimulated by specific antigen in lymphogranuloma venereum proctitis in nonhuman primates.

To study antigen-specific immune responses of gut-associated T lymphocytes after gastrointestinal infection, Cynomolgus monkeys were inoculated rectally with Chlamydia trachomatis of the L2 [lymphogranuloma venereum (LGV)] strain. Infected monkeys developed a chronic proctitis with the appearance of LGV-specific immunoglobulin G-antibodies in the serum. Lymphocytes isolated from the peripheral blood, the spleen, and draining lymph nodes had a vigorous antigen-specific proliferative response to LGV in vitro. Both T and B cells proliferated in response to stimulation with LGV, but B-cell proliferation was T-cell-dependent, as shown by cell separation techniques and cell-cycle analysis with dual-laser flow cytometry. Lymphocytes isolated from both involved and uninvolved lamina propria did not proliferate in response to LGV stimulation, whereas mitogen-induced proliferation was not different in lamina propria lymphocytes and the other lymphocyte populations. This lack of antigen-specific proliferation was not caused by a suppressor effect of mucosal T cells or monocytes or the absence of antigen-presenting cells. In contrast, lamina propria T lymphocytes from infected animals were able to provide antigen-specific help for polyclonal immunoglobulin synthesis by immune B lymphocytes after stimulation with LGV. Thus, in LGV proctitis in monkeys, mucosal antigen-reactive T cells differ from lymphocytes in other sites in that they can provide helper function, but are not able to proliferate in response to LGV antigens.

Animals↗