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Biomedical subjects

G Kraal

Publications and source records attributed to G Kraal.

At least 109 records · Page 6Linked to original sources
PubMed1991

Reduced frequency of nickel allergy upon oral nickel contact at an early age.

From animal studies we know that oral administration of T-dependent antigens before sensitization effectively induces systemic immune unresponsiveness. Such 'oral tolerance' is persistent, dose-dependent, antigen-specific and presumably T suppressor cell-mediated. Oral tolerance induction could be an effective way to prevent undesired T cell-mediated immune functions, such as playing a role in allograft reaction, autoimmune and allergic diseases. In the present study allergic contact hypersensitivity (ACH) to nickel, currently presenting the most frequent contact allergy in man, was chosen to establish the feasibility of oral prevention of undesired T cell-mediated immunity in man. Potentially tolerizing (oral nickel contacts via orthodontic braces) as well as sensitizing (ear piercing) events were studied retrospectively in 2176 patients attending nine European patch test clinics. Patients were interviewed by means of a confidential questionnaire. The results show that ear piercing strongly favoured development of nickel ACH. More importantly, patients having had oral contacts with nickel-releasing appliances (dental braces) at an early age, but only if prior to ear piercing, showed a reduced frequency of nickel hypersensitivity. Frequencies of other hypersensitivities, in particular to fragrance, were not affected. These results support our view that induction of specific systemic immunologic tolerance by timely oral administration of antigens is feasible in man.

Adolescent↗
PubMed1991

Mice bearing the E mu-myc and E mu-pim-1 transgenes develop pre-B-cell leukemia prenatally.

Previously, it has been shown that E mu-pim-1 transgenic mice are predisposed to T-cell lymphomas, whereas E mu-myc transgenic mice are predisposed to pre-B-cell lymphomas. Here we show that double-transgenic E mu-myc E mu-pim-1 mice exhibit pre-B-cell leukemia in utero. Upon transplantation into recipient mice, embryo-derived double-transgenic leukemic cells frequently progressed to highly malignant monoclonal tumors, indicating that additional (epi)genetic events had occurred during the progression of the disease.

Animals↗
PubMed1991

Expression of vascular addressins and ICAM-1 by endothelial cells in the spinal cord during chronic relapsing experimental allergic encephalomyelitis in the Biozzi AB/H mouse.

The expression of adhesion molecules on central nervous system (CNS) endothelia was examined during chronic relapsing experimental allergic encephalomyelitis (CREAE) in the Biozzi AB/H mouse. Active disease episodes (acute and relapse) were associated with the up-regulation of MALA-2, the murine homologue of intercellular adhesion molecule-1 (ICAM-1), on CNS endothelia and the infiltration of ICAM-1-positive mononuclear cells. In addition, the high endothelial venule (HEV)-associated MECA-325 antigen was evident in perivascular lesions, particularly in relapsing disease. The peripheral lymph node HEV-associated vascular addressin defined by MECA-79 antibody was not detectable in the CNS during CREAE. However, the mucosal HEV addressin was evident in lesions, which ultrastructurally was found to be expressed on the surface of endothelial cells by immunoelectron microscopy. The expression of adhesion molecules, such as ICAM-1, may provide a means by which both the initial neuroantigen-specific and the subsequent antigen-non specific cells extravasate into the CNS. Such infiltration may induce the expression of the vascular addressins which may then provide a means of site-selective cellular recruitment leading to disease progression.

Animals↗
PubMed1991

Alterations in dendritic cell phenotype and function associated with immunoenhancing effects of a subcutaneously administered cyclophosphamide derivative.

A single systemic dose of cyclophosphamide (CY) has been shown to enhance cellular immunity in a variety of antigen models. The immunoenhancing effects of CY have been attributed to its ability to selectively abrogate suppressor cell function. Previous studies from our group have demonstrated that local administration of distinct cytostatic drugs at the sensitization site can induce a similar enhancement of delayed-type hypersensitivity as systemic CY, with the obvious advantage of avoiding systemic side-effects. In the present study we investigated the effects of local administration of an optimally immunopotentiating dose of the active CY-derivative Z 7557 and, in selected experiments, of etoposide (VP-16) and systemic CY on mononuclear cells in draining lymph nodes. Whereas CY caused a long-lasting and marked depletion of B-cell areas, locally administered Z 7557 and VP-16 relatively spared B cells and even induced an increase in B- and T-cell numbers in (keyhole limpet haemocyanin-) sensitized mice. At Day 4 the CD4/CD8 ratio was slightly reduced in drug-treated mice. Interestingly, drug treatment reduced the proportion of interdigitating cells staining with the monoclonal antibodies NLDC-145 and MIDC-8. Upon isolation, dendritic cells (DC) from sensitized, Z 7557-treated mice showed longer dendritic protrusions and an enhanced accessory cell function compared to DC from saline-treated controls. These findings suggest that immunoenhancing effects of cytostatic drugs may occur via an effect on DC.

Adjuvants, Immunologic↗
PubMed1990

Spectophotometric quantification of cell-cell adherence by an enzyme-linked immuno-cell adhesion assay.

In the present study a spectophotometric method was developed to determine the number of T cells binding to human epidermal keratinocytes (KC). In this cell adhesion assay the adherent T cells were detected with a cell-specific monoclonal antibody conjugated to horseradish peroxidase and the coloured substrate quantified in an ELISA reader at 492 nm. A correlation was demonstrated between the number of T cells and the extinction values measured. The enzyme-linked immuno-cell adhesion assay (ELICAA) was used to quantify KC/T lymphocyte adherence in a series of experiments designed to evaluate its reliability and reproducibility. Compared with the 51Cr-labelled adherence assay, the ELICAA was a safe, rapid and accurate method avoiding the use of radioactive material.

Antibodies, Monoclonal↗
PubMed1990

Macrophages and the activity of high endothelial venules. The effect of interferon-gamma.

Interruption of the afferent lymphatic vessels of rat popliteal lymph nodes led to the disappearance of the monoclonal antibody ED3-reactive subcapsular sinus macrophages within 3 weeks, but had no effect on the ED1+ macrophages in the paracortical area. This disconnection of the afferent lymph flow to the popliteal lymph node also reduced the capacity of high endothelial venules (HEV) to bind lymphocytes and led to a flattening of the HEV. Activating factors or cells in the incoming lymph might be responsible for the maintenance and function of several different cell populations and we therefore wished to determine if the effects of interruption could be restored by injection of recombinant rat interferon-gamma (rIFN-gamma). Injection of rIFN-gamma directly into operated lymph nodes could mediate an apparent increase of ED1+ cells within 24 h but rIFN-gamma could not restore the macrophage subpopulation in the subcapsular sinus, as recognized by monoclonal antibody ED3. Restoration of the decreased binding capacity of HEV could not be observed with the doses and time points tested, suggesting that HEV are a distinct type of endothelium.

Animals↗
PubMed1990

Repopulation of macrophages in popliteal lymph nodes of mice after liposome-mediated depletion.

Macrophages lining the subcapsular sinus (SCS) and those located in the medulla of popliteal lymph nodes (PLN) of mice were eliminated after subcutaneous (s.c.) injection of dichloromethylene diphosphonate (Cl2MDP)-containing liposomes. No effect of liposome-entrapped Cl2MDP could be seen on nonphagocytic cells, e.g., interdigitating cells (IDC) and B- and T-lymphocytes. One month after injection the eliminated subsets of macrophages were still absent. After 2 mo a small number of macrophages had reappeared along the SCS and in the medulla of the PLN of a few animals. Complete repopulation of the PLN with macrophages was observed only after 5 mo. This extremely long repopulation time could be shortened drastically by local administration of Freund's complete adjuvant (FCA). A small number of macrophages reappeared along the SCS and in the medulla 1 wk after FCA and after 3 wk the repopulation of the PLN with macrophages was complete. Such rapid repopulation of macrophages was not achieved after s.c. injection of paraffin oil or paratyphoid vaccine. These results indicate that the normal rate of influx of mononuclear phagocytes into the PLN is low, but that it can be sped up after administration of FCA.

Animals↗
PubMed1990

Effect of genetically determined immunodeficiency on epidermal dendritic cell populations in C57BL/6J mice.

Mice homozygous for three different recessive mutations known to cause pleiotropic defects in the immune system and in the skin were used to evaluate the relationship between the classical immune system and dendritic epidermal cell populations. Numbers of Langerhans cells (LCs) and Thy-1+ dendritic cells (Thy-1+DEC) were determined using indirect immunofluorescence microscopy of epidermal whole mounts taken from viable motheaten (mev), nude (nu), and rhino (rhhr) mice. All mutants were maintained on the C57BL/6J strain background and were compared with their respective littermate normal controls. Viable motheaten mice had normal numbers of LCs at 1 month of age. However, by 8 weeks of age, LC density had decreased threefold. Nude and rhino mice had normal numbers of LCs at all ages tested. There was no significant effect of the viable motheaten mutation on numbers of Thy-1+DEC. Although nude mice showed normal numbers of Thy-1+ DEC at 1 month of age, these athymic mice had a threefold decrease in numbers of such cells by 6 months. In contrast to the reduced numbers of Thy-1+DEC seen in nude mice, rhino mice showed a four- to fivefold increase in the numbers of these epidermal cells at all ages tested. These findings suggest new mouse models for investigating the development, regulation, and biological properties of epidermal dendritic cell populations.

Animals↗
PubMed1990

The localization of macrophage subsets and dendritic cells in the gastrointestinal tract of the mouse with special reference to the presence of high endothelial venules. An immuno- and enzyme-histochemical study.

This study concerns the distribution of macrophages and dendritic cells (DC) in the gastrointestinal tract of the mouse. Heterogeneity of macrophage population was found by using the MOMA-1, MOMA-2, ERTR-9, Mac-1 and F4/80 monoclonal antibodies. MOMA-1, ERTR-9, Mac-1 and F4/80+ cells were detected mostly at the villous cores in the lamina propria of the villi, whereas MOMA-2+ cells were primarily found around the crypts at the base of the villi. These MOMA-2+ cells revealed a granular appearance throughout the cytoplasm and displayed a strong acid phosphatase (AcPh) activity. Few MOMA-2+ cells were seen at the top of the villi in the epithelium. Although MOMA-1 and ERTR-9+ cells have similar morphology and the same distribution patterns in the lamina propria, they are likely different populations, because in Peyer's patches (PP), MOMA-1+ cells were present, whereas ERTR-9+ cells could not be detected. Both populations displayed AcPh activity. Strongly stained Mac-1+ cells were abundantly seen in the lamina propria of the small intestine. F4/80+ cells were rare. NLDC-145+ cells with AcPh activity and weak Ia staining were also found. In the PP-associated villi and in the T-dependent area of PP, dendritic NLDC-145+ cells, which were strongly Ia positive, were detected. MIDC-8+ cells were found only in the T-dependent area. Few NLDC-145+ cells (dendritic cells) were found in the upper part of the oesophagus. These cells were also stained with the MIDC-8 antibody.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Functional capacities of high endothelial venules appear not to be controlled by recirculating lymphocytes.

The influence of recirculating lymphocytes on the function and morphology of high endothelial venules (HEV) has been studied. Mice were depleted of lymphocytes by lethal (1200 cGy) total body irradiation; subsequently, the HEV in mesenteric and cervical lymph nodes were studied up to 7 days after irradiation for: 1) capacity to bind lymphocytes by using the in vitro HEV-binding assay, 2) for morphological aspects such as ultrastructure and endothelial height, 3) for presence of RNA (pyroninophylia) and MECA-325 expression. Although, commencing 3 days after irradiation, lymphocyte depletion was intense and no extravasation of lymphocytes was observed; HEV were capable of binding lymphocytes at normal levels. Also the ratio of B/T cell binding to HEV was comparable to normal. MECA-325 expression, pyroninophilia, and ultrastructure of high endothelial cells were not affected by lymphocyte depletion. However, the average height of endothelial cells, which is a measurement related to cell volume, declined during lymphocyte depletion, stabilizing at about 70% of normal levels from day 4. After intravenous injection of viable lymph node cells, endothelial cell height rapidly increased within a few hours in conjunction with lymphocyte extravasation and homing into the nodes. Restoration of endothelial cell height was not observed after infusion of thymocytes, lethally irradiated lymph node cells or supernatants rich in cytokines. We conclude that recirculating lymphocytes in blood and lymphoid tissues are not involved in controlling high endothelial cell activity including the specific function in lymphocyte extravasation. However, recirculating/extravasating lymphocytes contribute to the development of endothelial cell height. The significance of non-lymphoid (radioresistant) cells in the control of characteristic high endothelial function is suggested.

Animals↗
PubMed1990

Different epitopes on the dendritic cell-associated NLDC-145 molecule during ontogeny.

A monoclonal antibody, 6D2, is described that recognizes a different epitope on the NLDC-145 dendritic cell associated molecule in the mouse. During ontogeny the epitope appears on interdigitating cells in lymphoid organs only around birth, whereas the NLDC-145 antigen can be detected as early as day 16 of gestation. No differences can be observed in the expression of the two antigenic determinants on the epithelial cells of the thymus during ontogeny. Evidence is presented that the two antibodies recognize different epitopes on the same molecule.

Animals↗
PubMed1990

Effect of aging on epidermal dendritic cell populations in C57BL/6J mice.

The density and function of epidermal dendritic cell populations were investigated in aged C57BL/6J mice. The densities of both Langerhans cells (LC) and Thy-1+ dendritic epidermal cells were found to decrease with age. Epidermal cell suspensions from aged mice showed impaired immunologic function as assessed in vitro by the skin-lymphocyte reaction assay and by measuring the ability of epidermal cell suspensions to stimulate the proliferation of sensitized T cells in the presence of the sensitizing antigen. However, the capacity of LC to transport antigen from the skin to the draining lymph nodes was found in vivo to be comparable to that of young mice. Results of transplantation of bone marrow cells from young and old donors into irradiated recipients indicate that the decreased Langerhans cell density found in old mice may result from a deficiency in Langerhans cell bone marrow progenitors.

Aging↗
PubMed1990

Effects of iodide on class II-MHC antigen expression in iodine deficient hyperplastic thyroid glands.

The expression of major histocompatibility complex class II molecules (Ia antigen) has been analyzed by immunoperoxidase staining in thyroids of normal C3H mice, of iodine-deficient mice with a hyperplastic goiter and of mice during goiter involution induced by administration of either a high iodide dose (HID, 10 micrograms/day) for 0.5 to 8 days or a moderate iodide dose (MID, 1 microgram/day) or triiodothyronine (T3, 1 micrograms/day) for 2 days. In normal and in hyperplastic thyroids, few interstitial cells were Ia positive (monoclonal antibodies, mAb, M5/114, ER-TR3). Their number was unchanged when goiter involution was induced by MID or by T3, but was significantly increased (p less than 0.05) after HID. It was maximal at days 1 and 2 of involution, decreased thereafter but remained higher (p less than 0.05) than in controls after 8 days. The Ia positive cells were mainly macrophages and, to a lesser extent, dendritic cells. Macrophages were identified by their heterogeneous content and their numerous lysosomes. They were stained with anti-Mac-1 (M1/70) and anti-Mac-2 (M3/38) mAb. Dendritic cells were characterized by their slender cytoplasmic processes, indented nucleus and pale cytoplasm. They were positive for NLDC-145 and MIDC-8 mAb whose specificity for dendritic cells has been demonstrated in lymphoid organs. During the whole period of involution analyzed, Ia antigens were not expressed on follicular cells. Since macrophages and dendritic cells are known to be involved in the pathogenesis of immune disorders, the inflammation induced by administration of HID to iodine-deficient mice could be considered as the early step of an immunological reaction.

Animals↗
PubMed1990

The function of high endothelial venules in mouse lymph nodes stimulated by oxazolone.

The effects of antigenic stimulation on the expansion of T-cell dependent areas in lymph nodes of mice were studied in relation to the effects on high endothelial venules (HEV) located in this area. Lymph nodes regional to areas of skin that had been treated with solutions of oxazolone were studied at several time-points after stimulation. The following measurements were made relative to lymph nodes of untreated animals: (i) the expansion of the T-cell dependent areas in combination with the increase of HEV in this area, as detected by the HEV-specific mAb MECA-325, using morphometric analysis: (ii) the influx of FITC-labelled lymphocytes from the blood into the lymph node by FACS: (iii) the capacity of HEV to bind lymphocytes using an in vitro binding assay. Morphometry showed that T-cell dependent areas increased rapidly after stimulation with oxazolone and although the mean area of MECA-325-positive HEV had also increased, this increase lagged behind the expansion of the T-cell area. Therefore the amount of HEV per T-cell area in an antigen-stimulated lymph node was smaller than in an untreated lymph node and correlated with the percentage of FITC-labelled cells that had entered it. In a lymph node from an oxazolone-treated animal this percentage was decreased to the same order of magnitude as the area of HEV per T-cell area, but the overall binding capacity of HEV was not affected by oxazolone treatment. Antigenic stimulation therefore leads to a rapid expansion of the potential sites of lymphocyte entry into a lymph node, but the efficiency of the HEV does not change.

Animals↗
PubMed1989

Alveolar macrophage elimination in vivo is associated with an increase in pulmonary immune response in mice.

A single intracheal dose of liposome-encapsuled dichloro-methylene-diphosphonate resulted in the elimination of alveolar macrophages (AM) from the lung, creating a model to study the in vivo role of AM in the pulmonary immune response. Using intratracheally administered trinitrophenyl-keyhole limpet hemocyanin (TNP-KLH), the kinetics of the response, the location and number of TNP-specific antibody-forming cells, and the different Ig classes of the antibodies produced were studied in AM-depleted animals. The results show that AM elimination has a dramatic effect on the pulmonary immune responses against TNP-KLH. An increase in APC in lung-associated lymph nodes and a prolongation of the response is found, as well as an introduction of APC in lung tissue. In both experimental groups, the majority of the TNP-specific antibodies produced was IgG, followed by IgA and IgE, while very few IgM antibodies could be detected. We conclude from these results that AM are likely to play a role in controlling the pulmonary immune response in a suppressive way, thereby limiting the possible damage caused by severe immune responses in lung tissue.

Animals↗
PubMed1989

Marginal zone macrophages and their role in the immune response against T-independent type 2 antigens: modulation of the cells with specific antibody.

Marginal zone macrophages are strategically positioned in the marginal zone of the spleen and are thought to play an important role in the initiation of the immune response to T-independent type 2 responses. The cells are characterized by high phagocytic activity and by the selective uptake of neutral polysaccharides. In the mouse marginal zone macrophages react specifically with the monoclonal antibody ER-TR9. Injection of the antibody resulted in a complete abrogation of the uptake of neutral polysaccharides by the cells in vivo, although the cells were still capable of taking up latex and carbon particles. The complete blockade of the polysaccharide uptake did not result in an altered humoral immune response against this antigen. When the antibody ER-TR9 was coupled to the toxin gelonin a complete elimination of the marginal zone macrophages could be established in vivo. However, complete elimination did not result in changes of the immune responses against 2,4,6-trinitrophenylated Ficoll, suggesting that the marginal zone macrophages are either not involved in this type of response, or that their function can be taken over by other cells. The possible role of these cells and the importance of the spleen in the immune response against bacterial antigens is discussed.

Animals↗
PubMed1989

The heterogeneity of the reticulum of rat peripheral lymphoid organs identified by monoclonal antibodies.

We have developed a panel of six monoclonal antibodies, ED10-ED15, directed against reticular cells in peripheral lymphoid organs. Immunohistochemistry revealed prominent differences between these antibodies with regard to their tissue distribution in lymphoid and non-lymphoid organs. Furthermore, the determinants recognized by ED10-ED13 were found to be differentially expressed by reticular cells occupying the various specialized compartments present in peripheral lymphoid organs. The reactivity patterns of these antibodies observed during the ontogenetic development of the spleen suggest that they recognize differentiation antigens expressed by reticular cells. In contrast, ED14 and ED15 were found to have a relatively ubiquitous tissue distribution recognizing reticular cells in each compartment, with a constitutive reactivity during splenic ontogeny. The present results indicate that reticular cells form a heterogeneous population within the lymphoid organs.

Age Factors↗