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G Kraal

Publications and source records attributed to G Kraal.

At least 73 records · Page 4Linked to original sources
PubMed1994

Dendritic cells of the oral mucosa and the induction of oral tolerance. A local affair.

The oral mucosa is an important site to induce immunological tolerance to protein antigens. Previously we have established that oral contacts to allergen can lead to systemic tolerance in both humans and experimental animals. Because of the importance of tolerance induction as a possible way to modulate allergic reactivity, we wished to study the mechanisms involved in efficient tolerance induction via the oral mucosa. Dendritic Langerhans' cells in both skin and oral epithelium are the first cells to encounter antigen. Therefore, possible functional differences between Langerhans' cells from skin and oral mucosa were studied by migration and transfer experiments. It was found that dendritic cells derived from the oral mucosa were not able to transfer tolerance, but that they acted as antigen-presenting cells in sensu stricto irrespective of the source and route of antigen administration.

Animals↗
PubMed1994

Enumeration of selected leukocytes in the small intestine of BALB/c mice infected with Cryptosporidium parvum.

Neonatal, suckling BALB/c mice inoculated with Cryptosporidium parvum produce an infection characterized by continuous shedding of oocysts that spontaneously clears by the time the animals are three weeks of age. Neonatal mice were used to characterize the leukocyte subgroups present in Peyer's patches from the ileum and jejunum of Cryptosporidium-infected and healthy mice. After infection, ileal Peyer's patches showed a predominant CD8+ response, with abundant monocytes-macrophages (MOMA-2+) and nonlymphoid dendritic cells (NLDC-145+ cells). In contrast, jejunal Peyer's patches showed more T lymphocytes than ileal patches, with a predominance of CD4+ cells and many dendritic NLDC-145+ cells and MOMA-2+ cells. The present results showed that ileal and jejunal Peyer's patches are functionally different in response to Cryptosporidium parasites. These findings suggest a preferential involvement of jejunal Peyer's patches in T cell-dependent immunity against the parasite, whereas ileal patches may be associated with B cell expansion and maturation.

Animals↗
PubMed1993

Downregulation of the antigen presenting cell function(s) of pulmonary dendritic cells in vivo by resident alveolar macrophages.

Class II major histocompatibility complex (Ia)-bearing dendritic cells (DC) from airway epithelium and lung parenchyma express low-moderate antigen presenting cell (APC) activity when freshly isolated. However, this function is markedly upregulated during overnight culture in a manner analogous to epidermal Langerhans cells. The in vitro "maturation" process is inhibited by coculture with pulmonary alveolar macrophages (PAM) across a semipermeable membrane, and the degree of inhibition achieved can be markedly increased by the presence of tumor necrosis factor alpha. In addition, PAM-mediated suppression of DC function is abrogated via inhibition of the nitric oxide synthetase pathway. Functional maturation of the DC is accompanied by increased expression of surface Ia, which is also inhibited in the presence of PAM. Prior elimination of PAM from DC donors via intratracheal administration of the cytotoxic drug dichloromethylene diphosphonate in liposomes, 24-72 h before lung DC preparation, achieves a comparable upregulation of APC activity, suggesting that (consistent with the in vitro data) the resident PAM population actively suppresses the APC function of lung DC in situ. In support of the feasibility of such a regulatory mechanism, electron microscopic examination of normal lung fixed by intravascular perfusion in the inflated state (which optimally preserves PAM in situ), revealed that the majority are preferentially localized in recesses at the alveolar septal junctions. In this position, the PAM are in intimate association with the alveolar epithelial surface, and are effectively separated by as little as 0.2 microns from underlying interstitial spaces which contain the peripheral lung DC population. A similar juxtaposition of airway intraepithelial DC is demonstrated with underlying submucosal tissue macrophages, where the separation between the two cell populations is effectively the width of the basal lamina.

Animals↗
PubMed1993

Macrophage phenotype regulation by colony-stimulating factors at bone marrow level.

Macrophages (m phi s) can be divided into several subpopulations, which differ in phenotype, function, and localization patterns. However, little is known about the mechanisms that regulate this heterogeneity. We investigated whether m phi heterogeneity is regulated by colony-stimulating factors (CSFs) at the bone marrow level. By clonal expansion of bone marrow-derived precursor cells in the presence of CSF-1, granulocyte-macrophage CSF or multi-CSF (interleukin-3), phenotypic heterogeneity was observed between m phi colonies. Heterogeneity was found especially when different CSF culture conditions were used but also between m phi colonies derived under the same CSF culture condition. Our results illustrate that CSFs from the bone marrow hemopoietic microenvironment are important for the induction of phenotypic heterogeneity within the progeny of cloned m phi precursor cells during maturation and differentiation in vitro.

Animals↗
PubMed1993

Migration of alveolar macrophages from alveolar space to paracortical T cell area of the draining lymph node.

In this report we studied the translocation of fluorescent particulate antigens to the draining lymph node, and the migration of fluorescent labeled alveolar macrophages (AM) and peritoneal macrophages (PM) in mice. The results show that intratracheally (IT) instilled particulate antigens translocate to the paracortical T cell area of the draining lymph node. When labeled AM were injected IT, they were found to migrate from the alveolar space into the paracortical T cell area of the draining lymph node. An identical localisation was found after IT injection of labeled PM. When either labeled AM, or PM were injected into the peritoneal cavity, a different migration pattern was observed. Via this route the labeled macrophages migrated to the subcapsular sinus and medulla of the draining lymph nodes. It is shown that the migrated cells are not dendritic cells (DC) present in the cell preparations. A possible role for the micro-environment of the injection site, and the significance of the specific migration pattern of AM is discussed.

Animals↗
PubMed1993

Developmental regulation of vascular addressin expression: a possible role for site-associated environments.

Tissue selective traffic of lymphocytes into different lymphoid organs is mediated by adherence of blood borne lymphocytes to specialized endothelial cells lining the high endothelial venules (HEV) in lymphoid organs. Lymphocytes discriminate between HEV in peripheral lymph nodes and in mucosal lymphoid tissues by means of membrane associated lymphocyte homing receptors adhering to their putative HEV ligands, the vascular addressins. The expression of particular vascular addressins on HEV is site- or tissue-selective and may be directed by factors unique to a specific location or lymph node environment. In this study we investigated the impact of regional environments on lymph node HEV differentiation and function. Experimentally, this problem was approached by the transplantation of lymph nodes from one region to a second region. The sites selected for receipt of tissues were the mesentery, a mucosal site, and the popliteal fossa, a peripheral site. We found that the phenotype of lymph node HEV following transplantation was influenced by both donor age and transplantation site. The transplantation site could influence vascular addressin expression, when tissues were obtained from late fetal or early neonatal donors and not when obtained from adult donors. Transplanted adult tissues retained their pre-transplantation vascular addressin expression phenotype regardless of transplantation site. Thus the endothelium within adult lymph nodes may be committed to expression of a particular addressin or addressins during lymph node development. It is also possible that regulatory cells or structures present within lymph nodes at the time of transplantation direct vascular addressin expression following tissue engraftment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Oral induction of tolerance to nickel sensitization in mice.

Antigen contact via the alimentary tract prior to sensitization may result in systemic immunologic unresponsiveness ("oral tolerance"). The induction of oral tolerance seems an attractive strategy to combat undesired immune responses, such as allograft rejection and autoimmune and allergic diseases. We describe clear and reproducible sensitization to nickel in mice reared under nickel-free conditions. Hypersensitivity was induced by injecting nickel sulfate intradermally into the flank skin and elicited by injecting the metal salt into the pinnae of the ears. The effectiveness of orally induced hyporesponsiveness could be inferred from a low degree of hypersensitivity obtained with mice raised and maintained in cages with nickel-releasing covers and water nipples. This mouse model for the assay of nickel hypersensitivity was used for oral tolerance studies by administrating non-toxic doses of nickel sulfate in drinking water or intragastrically prior to sensitization. In these animals, the development of delayed-type hypersensitivity was suppressed in a dose-dependent way, and the hyporesponsiveness could be transferred by CD8+ cells. The antigen specificity of this oral tolerance could be demonstrated by the concomitant use of sensitization and challenge procedures for nickel and chromium. The hypersensitivity assay described provides a versatile, highly reproducible experimental model to study immunoregulation of oral tolerance to clinically relevant metal allergens.

Administration, Oral↗
PubMed1993

Systemic elimination of macrophages using liposomes does not prevent the induction of type I diabetes.

Silica treatment of experimental animals leads to a prevention of genetically determined or experimentally induced type I autoimmune diabetes. Since silica is toxic for macrophages an important involvement of these cells in the onset of the disease was concluded. Here we show that in vivo elimination of macrophages by liposome treatment does not lead to prevention of streptozotocin-induced diabetes. The results indicate that the presence of mature macrophages is not an important requisite for diabetes induction and that the effects of silica treatment must be attributed to activation of macrophages leading to disturbed cytokine levels, or to effects on other cell types.

Animals↗
PubMed1993

Localization of beta 1 integrins and their extracellular ligands in human lymphoid tissues.

In this study, we describe the immunocytochemical distribution of the beta 1 integrins (alpha 1 to alpha 6) and their extracellular matrix ligands in human peripheral lymphoid tissues. The results show that within these tissues individual beta 1 integrins are differentially expressed by (sub)populations of stromal cells, including reticular cells, endothelial cells, epithelial cells, and sinus lining cells. The extracellular matrix components studied, eg, collagen I, III, and VI, fibronectin, laminin, and vitronectin, were predominantly associated with the stroma of the lymphoid tissues, and a unique distribution pattern was observed for each of them. Except for alpha 4 (and beta 1), low or no expression of the beta 1 integrins was found on lymphocytes, macrophages, interdigitating cells, and follicular dendritic cells. The results suggest that cell-matrix interactions play a major role in the maintenance of the complex spatial organization of the lymphoid tissue.

Child↗
PubMed1993

Regulation of T-cell function in lung tissue by pulmonary alveolar macrophages.

Collagenase digestion of perfused, lavaged rat lung yields a large population of CD5+ T cells, which on current evidence appear to be recently derived from the peripheral blood pool. Two-colour cytofluorographic analysis indicates that approximately 65% are CD4+ T cells, which are predominantly of the activated/memory phenotype. By limiting dilution analysis, these peripheral lung wall T cells and their airway counterparts isolated by bronchoalveolar lavage, exhibit markedly reduced capacity to proliferate by comparison to peripheral blood T cells. However, intratracheal inoculation of liposomes containing dichloro-methylene-diphosphonate at a dosage shown to eliminate the majority of resident alveolar macrophages (AM) rapidly restores the immunocompetence of these lung T-cell populations. These results are discussed in relation to recent reports that in vivo elimination of AM from rats and mice greatly amplifies immune responses to inhaled antigens, in particular T-memory cell-dependent secondary antibody responses.

Animals↗
PubMed1993

Establishment of bone marrow-derived macrophage cell lines by soft-agar cloning: regulation of macrophage heterogeneity at bone marrow level.

To study the regulation of macrophage (m phi) heterogeneity at bone marrow level, we developed a liquid culture system in which bone marrow-derived soft-agar colonies were expanded in the presence of colony-stimulating factor-1 (CSF-1). Several cloned m phi precursor cells were established as CSF-1-dependent cell lines, and were analyzed for morphological, phenotypic and functional characteristics. The continuously proliferating cell lines expressed both immature and mature m phi markers. Only minor differences between the established cell lines were detected. Thus, our results show that during long-term culture CSF-1-responsive cloned m phi precursor cells develop along identical pathways, giving rise to progeny with comparable phenotype and function in vitro.

Agar↗
PubMed1992

Identification of a soluble form of a ligand for the lymphocyte homing receptor.

Lymphocytes are engaged in constant trafficking from the blood into secondary lymphoid tissues, such as peripheral lymph nodes (PLN), mesenteric lymph nodes (MLN), and Peyer's patches (PP). The initial step in this process is the binding of lymphocytes to high endothelial venules (HEV), and in the case of trafficking of cells to the PLN, it is required that they bear the L-selectin surface receptor. Using a chimeric protein, combining the extracellular domains of L-selectin with a human immunoglobulin (Ig) G1 Fc region (L-selectin-IgG), we have probed the expression of ligands for this receptor on HEV and in cell lysates. Two sulfated glycoproteins of 50 and 90 kD have been identified in lysates from PLN and MLN, but not PP. Here we show that the 50-kD molecule is secreted in organ cultures in vitro and is present in the blood of normal animals. Indeed, normal serum inhibits lymphocyte binding to HEV by approximately 50% in an in vitro assay. This inhibitory activity can be removed by passage of the serum over an L-selectin-IgG column and has a molecular mass of approximately 50 kD. We speculate on the possible reasons for secretion of a homing receptor ligand.

Amino Acid Sequence↗
PubMed1992

Sialoadhesin on macrophages: its identification as a lymphocyte adhesion molecule.

In this study we present evidence that the mouse and rat sialoadhesin (originally named sheep erythrocyte receptor) on macrophages can function as a lymphocyte adhesion molecule. Lymphocytes were shown to bind to the splenic marginal zone, and lymph node subcapsular sinus and medulla in a frozen section assay. Selective depletion experiments showed that binding was mediated by macrophages. Adhesion was blocked by preincubation of the sections with monoclonal antibodies against mouse or rat sialoadhesin. Binding was temperature dependent, divalent cation independent, and involved sialic acid residues on the lymphocyte, as it could be inhibited by prior neuraminidase treatment or addition of the ganglioside GD1a. Binding to sialoadhesin was confirmed using the purified receptor and was observed among T cells, T blasts, B cells, and B blasts. Isolated macrophages or dendritic cells showed little binding. Sialoadhesin provides the first example of a macrophage-restricted lymphocyte adhesion molecule.

Animals↗
PubMed1992

Monoclonal antibody mediated targeting of enzymes. A comparative study using the mouse spleen as a model system.

The aim of this study was to target enzymes specifically to cells in the murine spleen. Monomeric and polymeric conjugates of the enzymes horseradish peroxidase or alkaline phosphatase and monoclonal antibodies against cell surface determinants were prepared. Highly specific in vivo targeting of enzymes to macrophages was obtained only when monomeric MAb-enzyme conjugates were used.

Alkaline Phosphatase↗
PubMed1992

Selective inhibition of immune complex trapping by follicular dendritic cells with monoclonal antibodies against rat C3.

The role of complement component C3 in the trapping of immune complexes by follicular dendritic cells (FDC) was studied in the rat, by means of the C3-specific monoclonal antibody ED11. Immunocytochemistry revealed the presence of C3 on FDC, where it co-localized with trapped peroxidase anti-peroxidase complexes. Furthermore, C3 was detected on reticular cells occupying the T cell areas of peripheral lymphoid organs, which are not involved in the handling of immune complexes. The in vivo administration of anti-C3 abolished the trapping of immune complexes in splenic follicles, but was unable to release preexisting complexes from the FDC. Trapping of immune complexes was also prevented by treatment of rats with cobra venom factor (CoVF). While CoVF caused massive depletion of C3 from serum, ED11 treatment had no such effect. The effect of anti-C3 appeared at least in part to be due to an inhibition of complement activation by immune complexes. We also analyzed earlier stages of the trapping process, with respect to their C3 dependence. Upon systemic injection immune complexes are initially observed in the marginal zone. Administration of anti-C3 reduced this localization, indicating a role for C3 in the entry of immune complexes into the spleen. Our results confirm experiments in CoVF-treated animals and extend the evidence for a role of C3 in the follicular trapping process using anti-C3 in vivo. The mechanism of immune complex trapping and the role of complement therein is discussed.

Animals↗