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PubMed1983

Lymphocyte subsets in normal human lymphoid tissues.

A series of B, T, natural killer (NK) cell, and monocyte-specific monoclonal antibodies was used to determine the localization of lymphocyte subpopulations in frozen tissue sections of human lymph node, spleen, tonsil, and thymus by means of an immunohistochemical technic. In thymus, most cortical thymocytes reacted with Leu 1, Leu 2a, Leu 3a, Leu 4, Lyt 3, OKT3, and OKT6 antibodies. Except for OKT6, Leu 2a, and Leu 3a, these antibodies also reacted with medullary thymocytes. The majority (70-80%) of medullary thymocytes reacted with Leu 3a and a smaller fraction (20-30%) with Leu 2a antibody. The staining pattern of thymic medulla approximates the staining pattern of peripheral T cells. In peripheral lymphoid tissues, the majority of cells in the paracortical region of lymph node and in the periarteriolar sheath of spleen stained with Leu 1, Leu 4, OKT3, and Lyt 3 antibodies. Staining with Leu 3a and Leu 2a identified 60-80% and 20-40% of total T cells, respectively, as defined by Lyt 3 positivity. In addition, a substantial number of Leu 3a+ and Leu 7+ cells were found in the germinal centers of secondary follicles. This finding supports the importance of these subsets of lymphocytes in regulation of the human immune response. Leu 2a+ cells were rare in tissues with prominent follicular hyperplasia, but appeared in considerable number in the red pulp of spleen. In the mantle zone of lymphoid follicles, the majority of lymphocytes were positive for IgM, IgD, and B1. Approximately 60-70% of these cells bore kappa chain and 30-40% lambda chain immunoglobulin. The extracellular substance in germinal centers was positive for B1, IgG, IgM, kappa, and lambda. The majority of germinal center cells appeared to contain no surface or cytoplasmic immunoglobulins. Small mononuclear cells bearing OKM1 marker were abundant in the marginal zone of white pulp and in the red pulp of spleen but, rarely were observed in other portions of lymphoid tissues. OKM1 also reacted with granulocytes. Leu 7+ (NK) cells were rare in the thymus, but frequent in the GC of secondary follicles. The distribution of Leu 7+ cells did not correspond to staining with Lyt 3 and Leu 2a.

Antibodies, Monoclonal↗
PubMed1983

[Morphofunctional changes in the lymphoid tissue of the respiratory organs in gamma-globulin administration].

By means of macro-microscopic, histologic, radioautographic and immunomorphologic methods, three forms of the lymphoid tissue structural organization have been revealed in the rat respiratory organs: a lymphoid cluster, a lymphoid follicle and a lymphoepithelial nodule. After gamma-globulin is administered intranasally, the ratio of the lymphoid cells in the organs mentioned changes: the number of small lymphocytes decreases, while that of middle, large lymphocytes and blast cells increase. The lymphoid follicles consist of a central and a marginal zones, in the lymphoepithelial nodules the subepithelial and paranodular zones also exist. The gamma-globulin administration stimulates DNA synthesis by the cells of the lymphoid type and their proliferation; that results in increasing number of the antibody-synthesizing cells and is accompanied with an increasing titre of antibodies in washing from the bronchial tree. At a repeated stimulation, the processes are more intensive and develop more quickly.

Animals↗
PubMed1993

Primary low-grade B-cell lymphoma of the conjunctiva: a mucosa-associated lymphoid tissue type lymphoma.

We describe the clinical presentation, morphology, immunophenotypic features and molecular biology of seven cases of conjunctival lymphoid infiltration. In five cases there was either immunophenotypic or molecular evidence of B-cell lymphoma. Each of these cases showed the morphological, immunophenotypic and molecular feature of low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type. The findings suggest that most conjunctival lymphomas are of this type and explains their uniformly favourable prognosis.

Adult↗
PubMed1995

Segmented filamentous bacteria associated with lymphoid tissues in the ileum of horses.

Segmented filamentous bacteria preferentially attached to the follicle-associated epithelium overlying the lymphoid tissue in samples of the terminal ileum from seven horses examined by scanning electron microscopy. The bacteria adhered to the apical membrane of the enterocytes by a holdfast segment. Each filament tended to be of uniform diameter, but the filaments ranged from 0.7 to 1.4 microns in diameter. The bacteria were usually absent from the adjacent villous epithelium.

Animals↗
PubMed2001

Characterization of ovine nasal-associated lymphoid tissue and identification of M cells in the overlying follicle-associated epithelium.

The distribution of mucosal lymphoid nodules in the ovine nasopharyngeal tract was studied by an acetic acid fixation technique. Nodules, which were concentrated just posterior to the opening of the Eustachian tube, were excised and examined by light microscopy, and scanning and transmission electron microscopy. Immunohistochemical examination revealed that each lymphoid structure consisted of follicles containing discrete B- and T-cell areas, characteristic of a mucosal inductive site of the mucosa-associated lymphoid tissue (MALT). Electron microscopy revealed that specialized epithelial cells, displaying features characteristic of M cells, were present in the follicle-associated epithelium (FAE) that covered the lymphoid nodules. These cells had sparse irregular microvilli and were closely associated with lymphocytes in the underlying tissue. These findings suggest that targeting the nasopharyngeal region may provide a practical and effective route for the stimulation of protective mucosal immune responses.

Acetic Acid↗
PubMed2001

Lymphoid neogenesis: de novo formation of lymphoid tissue in chronic inflammation through expression of homing chemokines.

Chronic inflammation is a complex pathophysiological process with accumulation of mononuclear cells seen in response to invading pathogens, neoplastic transformation, or autoimmune recognition of self-antigens. The inflammatory process has evolved to facilitate effective elimination of pathogens and tumors and it is normally transient and turned off when the causative stimulus has been eliminated. Occasionally, however, the process is sustained for a long time and can lead to severe tissue damage. This is seen in organ-specific autoimmune diseases such as rheumatoid arthritis, Sjögren's syndrome, and Hashimoto's thyroiditis, but also in infectious diseases such as Helicobacter pylori-induced gastritis. Disturbingly, many of these chronic inflammatory diseases are associated with an increased risk for neoplastic transformation and development of lymphomas. This review summarizes experimental evidence suggesting that chronic inflammation involves ectopic de novo formation of organized lymphoid tissue and that this lymphoid neogenesis is regulated by expression of homing chemokines.

Animals↗
PubMed1979

Bronchus-associated lymphoid tissue (BALT) in the laboratory-bred and wild rat, Rattus norvegicus.

In juvenile wild rats, bronchus-associated lymphoid tissue (BALT) development was similar to that seen in adult specified-pathogen-free rats. In adult wild rats the BALT was widespread. In one animal infected with a mycoplasma-like organism, a region of bronchoepithelium overlying a large BALT nodule was seen, through which lymphocytes appeared able to pass to make direct contact with the bronchial lumen: the significance of this observation is discussed. There was no evidence of infection in lungs from any of the specified-pathogen-free animals, where small foci of BALT were seen.

Animals↗
PubMed1980

Immunohistologic analysis of the organization of normal lymphoid tissue and non-Hodgkin's lymphomas.

Hoping to improve the systems for identifying and classifying normal and malignant lymphoid subpopulations, frozen and paraffin sections of nonmalignant lymphoid tissue and of malignant lymphomas were immunostained for surface (S) and cytoplasmic antigens using the peroxidase-antiperoxidase method. Primary follicle cells and follicle mantle cells known to be part of the recirculating B-cell pool were found to be constantly Ia and C3 receptor (C3R) positive, mostly SIgM and SIgD positive and cytoplasmic immunoglobulin (CIg) negative. The light zone of germinal centers (GC), which is rich in centrocytes, contained a large number of T cells and showed the well-known intercellular Ig network pattern; the dark zone, containing densely packed centroblasts, was usually free of T cells, but was bordered ay a mantle-like accumulation of T cells. Usually only some of the GC cells were definitely positive for SIg and CIg of different classes. All cells reacted positively for Ia and C3R. In areas described by other authors as containing marginal zone cells, cells densely bearing SIgM and deficient in SIgD were detected. The immunoblasts of the hyperplastic plasma cell reaction usually contained CIg. Cells from chronic lymphoid leukemia sections that immunostained for SIgM and SIgD were interpreted as representing a neoplasm of recirculating B cells expressing SIgM and SIgD. The immunohistologic architecture of follicular centroblastic/centrocytic lymphoma showed a more or less close similarity to the organization of secondary follicles. Lymphomas whose cells resembled reactive centrocytes were strongly SIgM positive and SIgD negative or only weakly SIgD positive. CIg was demonstrable in nearly 90% of the lymphomas whose cells resembled centroblasts and in 70% of the lymphomas whose cells resembled immunoblasts of the plasma cell reaction. Finally, immunohistologic staining results from a T-zone lymphoma are presented, which confirm that this lymphoma was composed of a neoplastic T zone and a non-malignant B zone.

Antigens↗
PubMed1983

Development of bronchus associated lymphoid tissue (BALT) in the rat, with special reference to T- and B-cells.

The development of bronchus associated lymphoid tissue was studied in normal rats, in serial sections, using both routine histological techniques and the two-step immuno-peroxidase method on cryostat sections for demonstration of T lymphocytes, IgM-, IgG- and IgA-bearing B lymphocytes and plasma cells, respectively. BALT first appears 4 days postpartum (p.p.) as a condensation of reticulum cells near a lymph vessel, between the main bronchus and the accompanying artery. Only a few lymphocytes are present at first. Vascularisation is considerable 8 days p.p. and includes high endothelial venules. Leucocytes are seen in transit in both blood- and lymph vessel walls. Lymphocytes populate the area under the epithelium from about 2 weeks p.p. A few IgM, IgG- and IgA-bearing B cells are already present at 4 days, and rapidly increase in numbers; T cells usually appear at day 8. Discrete T- and B-cell areas do not appear until 4 weeks and are only observed regularly after 12 weeks, when secondary follicles appear. BALT starts development at a similar time to other peripheral lymphoid organs but apparently achieves immunological activity later. It is concluded that antigens probably play an important part in organising BALT.

Age Factors↗
PubMed1986

Presence of interferon in venous blood draining from gut-associated lymphoid tissue.

The question has been examined of whether interferon (IFN), produced in the microenvironment of the gut-associated lymphoid tissue (GALT) during the physiological response, is consumed locally, or whether some spills over and is drained into the general circulation. Plasma IFN levels were measured in venous blood draining from abdominal organs that are normally in contact with exogenous and endogenous interferon inducers. The results obtained from three rodent species indicate the presence of a venous-arterial and GALT venous-peripheral venous gradient, suggesting that at least some of the IFN produced in the GALT and spleen is absorbed via blood capillaries and detectable in the regional vessels. Owing to the rapid turnover of IFN, arterial or peripheral venous blood showed a basal level. The antiviral activity (AA) in rat and mouse blood appears to be attributable to IFN-gamma.

Animals↗
PubMed2000

[Basic and clinical aspects of bronchus-associated lymphoid tissue].

Human mucosal membrane surfaces have a distinct protective mechanism that is specifically designed to produce secretory IgA. In the airway, bronchus-associated lymphoid tissue (BALT), is known to be an inductive site of secretory IgA. BALT is a lymphoid aggregate located in the submucosal area of bronchioles, and plays a central role in airway mucosal immunity by inducing the accumulation of secretory IgA-producing cells. Although previously it had been unclear whether BALT is present in the human lung, we demonstrated the expression of BALT in patients with diffuse panbronchiolitis, chronic hypersensitivity pneumonitis, and collagen disease-associated lung diseases. BALT was shown to elevate serum IgA levels and in other ways to have an influence on the symptoms and signs in patients with these pathologic conditions. We also demonstrated that continuous inhaled antigenic stimulation as well as the local production of interleukin-4 and other cytokines promote BALT development, which, in turn, may give rise to BALToma, a type of primary pulmonary mucosa-associated lymphoma.

Animals↗
PubMed1980

I. Immunosurveillance and tumorigenesis in 1. BALB/c mice. Early reactive state in the jejunum disseminated lymphoid tissue.

Using functional ultrastructure we established the physiology of the cellular immune response in the BALB/c mouse jejunum disseminated lymphoid tissue (JDLT) before and after sequential stimulations with E. coli endotoxin (ECE) (the preceding article in this journal). The functional ultrastructure was established also in this series of BALB/c mice injected i.p. initially with 0.5 ml of mineral oil and then weekly with 5 ng of ECE (EOA). The present series of mice had a pathological immune response and, it is known that they will in time produce plasmacytomas. Differences between the physiologic and pathologic immune responses during the first month of tumorigenesis, are: 1. The T-lymphocyte response was found to be strong but disorganized; 2. As judged from the T:B ratios, the B-lymphocyte response was found to be very strong, late after the first, early after the second, and late after the fourth injections with ECE, in this EOA model of stimulation. 3. The macrophage cellular response during the EOA stimulation was found to be slightly weaker than that seen in the series of mice stimulated with ECE alone. At the time of this study, the differences found between the physiologic and pathologic immune responses in the JDLT are not conclusive and they do not elucidate either the mechanisms of tumorigenesis or the role of the immunocompetent cells.

Animals↗
PubMed1991

Different bcl-2 protein expression in high-grade B-cell lymphomas derived from lymph node or mucosa-associated lymphoid tissue.

High-grade B-cell lymphomas, whether originated in a lymph node or in mucosa-associated lymphoid tissue (MALT), show similar morphologic traits, a fact that has fueled a long-running controversy about whether they represent different entities. They differ, however, in that some high-grade MALT lymphomas show less aggressive clinical behavior, a focal low-grade component being identified in some of them. In a search for bcl-2 protein expression, we have found a significant difference between nodal (39/48) and MALT high-grade B-cell lymphoma (1/15) (P less than 0.01). Bcl-2 gene product is an inner mitochondrial membrane protein able to give a survival advantage to B-cell lines by blocking programmed cell death. This protein is usually expressed by memory or resting B cells, most activated B cells being bcl-2 negative, except in lymph-node-originated high-grade B-cell lymphomas, which appear to be mainly bcl-2 positive. Presence of bcl-2 protein in nodal large-cell lymphomas seems to be independent of a t(14;18) translocation, only being found in 19 to 28% of these lymphomas, although it constitutes a definite difference between both tumors, suggesting the existence of different molecular genetic characteristics and pathogenesis, and is possibly related to the more aggressive clinical behavior of nodal high-grade tumors.

Cell Transformation, Neoplastic↗
PubMed1993

[A clinicopathologic study of primary gastric lymphoma of B-cell type among the Japanese with special reference to low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT)].

The most common primary site of low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is the gastrointestinal tract, particularly the stomach. The relationship of MALT lymphomas, however, with the more commonly occurring large B-cell gastric lymphoma has not been directly discussed except in the report of Chan et al. (1990), which lacked clinical information regarding the behavior of these tumors. To elucidate the relationship between high-grade large-cell lymphoma and MALT lymphoma, we studied in detail the histopathological and clinicopathologic features with the survival date of 77 Japanese cases of primary gastric lymphoma (PGL) of B-cell type. Based on degree of morphologically recognizable low- or high-grade components of the tumor, PGL was divided into four types: 18 cases of pure MALT lymphoma (type I); 13 cases of MALT lymphoma with small area of high-grade lymphoma (type II); 22 cases of high-grade lymphoma with small areas of MALT lymphoma (type III); and 24 cases pure high-grade lymphoma (type IV). Corresponding to the differences in the histologic pictures of each type, there were differences in the gross appearance, pathologic stage (including depth of invasion) and prognosis. These data suggests that both MALT and high-grade lymphomas of the stomach belong to the same cell lineage and constitute a pathological spectrum and that the histological grouping of PGL is clinico-pathologically useful.

Adult↗
PubMed1997

Organ culture of human lymphoid tissue. II. Marked differences in cytokine production and proliferation between slice and suspension cultures of human spleen.

Recently, we have established a method for the culture of human spleen slices in vitro. The procedure allows thin slices (200-350 microns) of human spleen to be cultured for up to 7 days. Using this method, we have previously established that unstimulated spleen slices spontaneously synthesize and secrete considerably higher levels of immunoglobulin than suspension cultures of the same tissue run in parallel. In this study, we report that there are also marked differences in the cytokine secretion profile between slices and suspensions and in their proliferative response. In brief, control and PHA-stimulated spleen slices secrete high levels of IL-1 beta, IL-6, IL-8 and IL-11 while the levels found in suspension supernatants are appreciably lower. By way of contrast, high levels of IL-2, IL-4, IL-10 and TNF alpha are found in suspension culture supernatants following PHA stimulation while the response in slice cultures is extremely low. These differences are also reflected in the results obtained at the cellular (intracellular cytokine) level. Additional studies reveal that spontaneous immunoglobulin production observed in spleen slices can be inhibited by the addition of specific antibodies to IL-1 beta, IL-6 and TNF alpha and that the bulk of the IL-6 and IL-1 beta detected in culture supernatants represents de novo synthesis. Finally, the background and mitogen-stimulated proliferative response of tissue slices is meagre compared with that observed in spleen suspensions suggesting that proliferation in the former is held under strict control. Collectively, we believe that the tissue slice procedure described provides us with a system for studying integrated events in lymphoid tissues in vitro and evaluating immunomodulatory substances of potential clinical importance.

Adolescent↗
PubMed1985

Noradrenergic and peptidergic innervation of lymphoid tissue.

Sympathetic noradrenergic nerve fibers innervate both the vasculature and parenchymal fields of lymphocytes and associated cells in several lymphoid organs, including the thymus, spleen, lymph nodes, gut-associated lymphoid tissue (GALT), and bone marrow, in a variety of mammalian species. This innervation is both regional and specific, and generally is directed into zones of T lymphocytes and plasma cells rather than into nodular regions or B lymphocyte regions. In the thymus, noradrenergic fibers enter with nerve bundles and plexuses around blood vessels, travel into the cortex from subcapsular plexuses and with the vasculature, and branch into the parenchyma of the thymic cortex. The vasculature and parenchymal regions of both the outer and deep cortex are innervated by these fibers. In the spleen, noradrenergic fibers enter with the vasculature, travel along the trabeculae and along the branching vasculature, and are distributed mainly in the white pulp along the central artery and associated periarterial lymphatic sheath. Fibers branch from a dense plexus around the central artery and travel into the parenchyma, where they end among fields of lymphocytes and other cell types. In lymph nodes, noradrenergic fibers enter at the hilus, travel along the vasculature and in a subcapsular plexus, and branch into the parenchyma in paracortical and cortical regions, where they end among lymphocytes. In the GALT, represented in these studies by rabbit appendix, sacculus rotundus, and Peyer's patches, noradrenergic fibers enter at the serosal surface, travel longitudinally with the muscularis interna, turn radially into internodular plexuses, plunge directly through the thymus-dependent zones, and ramify profusely among lymphocytes, enterochromaffin cells, and plasma cells in the interdomal regions. In the bone marrow, noradrenergic fibers enter with blood vessels, distribute deeply into the marrow on those vessels, and branch sparsely into the substance of the marrow. Immunocytochemical observations revealed the presence of neuro-peptide-like immunoreactivity in the thymus and spleen. Vasoactive intestinal peptide (VIP)-like immunoreactivity is found in varicose profiles in the thymus within the cortex. In the spleen, immunoreactive profiles showing neuropeptide Y-like, Met-enkephalin-like, cholecystokinin-8 (CCK)-like, and neurotensin-like immunoreactivity are present along the central artery of the white pulp and its smaller branches, with only sparse fibers of most of these peptides entering the parenchyma. CCK-like profiles are present in abundance in the white pulp among parenchymal elements.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenergic Fibers↗
PubMed1985

Immunohistochemical analysis of the distribution of vimentin in human peripheral lymphoid tissues.

The distribution of the intermediate filament protein vimentin in peripheral lymphoid tissues was determined using a monoclonal antibody. Frozen sections of tissue were stained using an avidin-biotin immunoperoxidase method. The antibody stained endothelial cells in spleen, lymph node, and tonsil. Unusual rod-like structures were revealed in the sinusoid-lining cells of the spleen. A variety of reticulum cells was detected, including fibroblastic reticulum cells, histiocytic reticulum cells (tingible body macrophages), and splenic marginal zone macrophages. Very few lymphocytes were immunoreactive. Only weak cytoplasmic immunoreactivity was observed in lymphocytes of the periarteriolar lymphocyte sheath of the spleen. The monoclonal antibody employed appears to be of limited usefulness in detecting normal lymphocytes, but is strongly reactive with endothelial structures and some types of reticulum cells.

Histocytochemistry↗