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PubMedDate not supplied

Comparative anatomy of mammalian conjunctival lymphoid tissue: a putative mucosal immune site.

Organized mucosa-associated lymphoid tissue (O-MALT) is defined by mucosal lymphoid follicles with unique overlying lymphoepithelia, and classically appears in tissues with a simple columnar epithelium. Within follicle-associated epithelium, goblet cells are characteristically absent, replaced by ultrastructurally distinct antigen-absorptive cells, termed M cells (or microfold cells) for the appearance of their apical cell membranes. To determine if mammalian conjunctiva, with its stratified squamous epithelium, can be considered as a site of O-MALT, we compared the light and electron microscopic anatomy of conjunctiva from fourteen species of non-human adult mammals, and the conjunctiva of human adults harvested at autopsy. Lymphoid follicles in the conjunctiva were demonstrated in all mammals studied except for mice and rats. In those mammals with conjunctival lymphoid follicles, the follicle-associated conjunctival epithelium was notable for an absence of goblet cells. Transmission electron microscopy demonstrated an intimate association of lymphocytes with surface epithelial cells, but epithelial cell morphology was uniform overlying the follicle, and other ultrastructural features of M cells were absent. Therefore, conjunctival lymphoid follicle-associated stratified squamous epithelium demonstrates some but not all features of O-MALT lymphoepithelia. Further studies are necessary to determine what role conjunctival lymphoid tissue may play in mucosal immunity.

Adult↗
PubMed1981

Functional studies on histiocytic and interdigitating reticulum cells from human lymphoid tissue.

Histiocytic (HRC) and interdigitating (IDC) reticulum cells were obtained from human lymphoid tissue (lymph nodes, tonsils), suspended in cell culture medium and cultured. The suspended cells, which were identified by morphological and enzyme histochemical criteria, were studied for surface binding properties for Fc-receptors using erythrocytes coated with IgG. HRC show strong surface binding, IDC, somewhat weaker, but definitely positive surface binding. Both types of reticulum cells possess Fc-receptors; on IDC, however, they are fewer in number and less dense. In connection with recently discovered Fc-receptors on Langerhans cells of the epidermis, functional relationships between blood monocytes, Langerhans cells in skin and IDC in lymphoid tissue are discussed.

Histiocytes↗
PubMed1991

Tumour necrosis factor receptor distribution in human lymphoid tissue.

The nature and location of cells responding to tumour necrosis factor-alpha (TNF-alpha) were investigated in situ by immunohistochemistry using monoclonal antibodies (mAb) directed against the p75 and p55 proteins of the TNF receptor. Receptor expression was found in the thymus and secondary lymphoid tissues. In the thymus the p75 receptor was confined to medullary lymphoblasts and dendritic cells, which co-stain with the Tac protein of the interleukin-2 (IL-2) receptor. In lymph nodes and other secondary lymphoid tissues, the p75 receptor was expressed on activated lymphocytes and interdigitating reticulum cells of the T-cell area, whereas the p55 receptor was confined to the germinal centre dendritic reticulum cells (DRC), which is the main site of TNF-alpha production. TNF receptor (TNFR) proteins were up-regulated in reactive hyperplasia together with increased TNF-alpha expression. Surprisingly, no TNFR was detectable on non-lymphoid tissues. The species specificity of these TNFR antibodies was high: whereas the antibodies cross-reacted with epitopes in non-human primates, no immunoreactivity was detected in lower animal species, e.g. dog, rabbit and rodents. The data presented suggest that TNF-alpha, which is produced by germinal centre DRC, might regulate an in vivo immune response through autocrine and paracrine pathways, e.g. through the p55 and p75 receptor proteins, which are expressed at different sites of the lymphoid tissue.

Animals↗
PubMed2000

Expression of inflammatory cytokine mRNA in lymphoid tissue from swine experimentally infected with Mycobacterium avium serovar 2.

OBJECTIVE: To evaluate in situ expression of inflammatory cytokine mRNA in lymphoid tissue of swine experimentally infected with Mycobacterium avium serovar 2. ANIMALS: 7 noninfected pigs and 7 pigs infected with M. avium serovar 2. PROCEDURE: Expression of mRNA of inflammatory cytokines such as tumor necrosis factor alpha (TNFalpha), interleukin (IL)-1beta IL-6, and IL-8 in formalin-fixed paraffin-embedded blocks of lymphoid tissue (lymph nodes and tonsil) of swine experimentally infected with M. avium serovar 2 was compared with that of noninfected pigs. Tissues were evaluated by use of morphologic localization of cytokine mRNA, using in situ hybridization at 160 days after inoculation. RESULTS: A noticeable increase in mRNA expression for TNFalpha and mild increases in mRNA expression of IL-8 and IL-1beta were detected in mandibular lymph nodes from infected swine, compared with noninfected swine. Mild increase in mRNA expression for 1L-6 also was observed in tonsils from infected swine. Cytokine mRNA was detected in macrophages and lymphocytes, primarily within cortical follicles and adjacent mantle zones. CONCLUSIONS AND CLINICAL RELEVANCE: Expression of mRNA for inflammatory cytokines was increased in lymphoid tissue of infected swine, possibly resulting from local factors on, or secreted by, M. avium. These results suggest that alterations in cytokine mRNA expression are important in the pathogenesis and clinical course of mycobacteriosis in swine. Modulation of the immune response by vaccines that selectively target cytokine expression and secretion in response to mycobacterial challenge may be effective in prevention of mycobacteriosis in swine.

Animals↗
PubMed2002

Histological and immunohistochemical study of the lymphoid tissue in the normal stomach of the gnotobiotic pig.

Animal models have been developed in which the role of Helicobacter pylori in the pathogenesis of different gastroduodenal diseases can be investigated. The gnotobiotic pig was one of the first animal models used. In this model, Helicobacter pylori infection causes gastritis, which shows some similarities to that in humans, such as the development of mucosa-associated lymphoid tissue (MALT). Hence, this animal model can be used to study the development of MALT in the normal stomach. The aim of our study is to see if lymphoid tissue is present or absent in the normal stomach of gnotobiotic pigs before birth and if so, to investigate its development and composition as a function of gestational age and location in the stomach. Therefore, we studied 82 foetal piglets using routine histology and immunohistochemistry. Our findings show that lymphoid tissue is present at birth. It is composed of lymphoid nodules, a diffuse mononuclear infiltrate and intra-epithelial lymphocytes. The development is a sequential process. The lymphoid tissue in the stomach at birth is composed of the immunohistochemically different immunocompetent cells normally present. In conclusion, MALT is present in normal foetal gnotobiotic pig gastric mucosa, and in this model the stomach is no exception to the rest of the gastrointestinal tract.

Animals↗
PubMed1994

Heterogenous Na+, K(+)-ATPase expression in the epithelia of rabbit gut-associated lymphoid tissues.

Na+, K(+)-ATPase expression in the epithelia of rabbit gut-associated lymphoid tissue was measured using indirect immunofluorescence and confocal laser scanning microscopy. All four major sites of aggregated lymphoid tissue, i.e. Peyer's patch, sacculus rotundus, caecal patch and appendix, were studied. Na+, K(+)-ATPase expression was localized to the basolateral surface of cells of the follicle-associated epithelium (FAE) and adjacent villous or surface epithelia (non-FAE), where increased expression during enterocyte migration was evident. In the FAE, expression of Na+, K(+)-ATPase appeared to be lower in the specialized M cells than in enterocytic-type cells, although expression in both cell types was lower than in adjacent non-FAE. Quantification of immunofluorescent staining of Na+, K(+)-ATPase by confocal laser scanning imaging showed a reduction of expression in the FAE to approximately 20-60% relative to that in the adjacent non-FAE. These results are consistent with a primary role of the FAE in mucosal immunity with minimal involvement in active solute absorption.

Animals↗
PubMed1999

Polyamine oxidase activity in lymphoid tissues of glucocorticoid-treated rats.

Glucocorticoids are known to negatively affect lymphoid tissues, in which they cause programmed cell death. Polyamine depletion, which occurs in glucocorticoid-treated animals by inhibition of biosynthesis and induction of acetylation, may represent a signal to thymocytes for progression into the apoptotic program. Since catalysis of polyamines by the catabolic pathway produces hydrogen peroxide as a by-product, it has been suggested that the apoptotic process may be, in part, due to oxidative stress as a result of hydrogen peroxide production. In order to verify whether polyamine oxidase (EC 1.5.3.11) may play a role in the process, we examined the activity of the enzyme in the thymus and spleen of glucocorticoid-treated rats. We administered dexamethasone (4 mg/kg) or two different doses of corticosterone (4 mg/kg or 30 mg/kg) to rats, which were killed 8 or 24 hr after hormone injection. We found that corticosterone and dexamethasone affected polyamine oxidase activity in both tissues, with an opposite dose-dependent effect of the natural hormone in the thymus. The decrease and increase in polyamine oxidase after the two doses of corticosterone were correlated with the absence and the occurrence of DNA fragmentation, respectively. Moreover, corticosterone affected polyamine oxidase activity earlier (8 hr) than dexamethasone (24 hr), but the synthetic hormone was more efficient than the natural hormone in thymic polyamine depletion. The polyamine oxidase response may represent an important event in lymphoid tissues after glucocorticoid treatment, suggesting a role of the enzyme in the catabolic effects exerted by the two hormones.

Animals↗
PubMed1990

Is the bronchus-associated lymphoid tissue (BALT) an integral structure of the lung in normal mammals, including humans?

In the respiratory tract, lymphoid aggregates with a specialized epithelium have been called bronchus-associated lymphoid tissue (BALT) and compared to the organized lymphoid tissue of the gut (GALT), e.g., Peyer's patches. BALT might play a central role in antigen uptake, initiating immune responses and disseminating primed lymphoid cells in the respiratory tract. In the present study, lungs of mice, rats, guinea pigs, rabbits, pigs, cats, and humans have been studied with respect to the presence and number of BALT and the dependence of BALT on age and microbial stimulation. BALT is not a constitutive structure in all these species. Its frequency varies widely, from 100% in rabbits and rats, 50% in guinea pigs, 33% in pigs, to its absence in cats and all normal human lungs. BALT seems to be a lymphoid structure which is not present in all the species studied but can develop in the lung after stimulation. This is in contrast to lymphoid organs, such as lymph nodes or Peyer's patches, which can always be found. These species differences are of major importance in interpreting the clinical relevance of experiments in animal models on the lung immune system, e.g., antigen uptake, immunostimulation, or lung transplantation.

Aging↗
PubMed1996

Bilateral mucosa-associated lymphoid tissue lymphomas of parotid glands: a 13-year interval.

Benign lymphoepithelial lesions of salivary gland may have a population of monoclonal B cells. There is controversy regarding the clinical significance of monoclonality in these lesions. Morphologically and clinically, benign lymphoepithelial lesions of the salivary gland with monoclonal B cells falls within the spectrum of low-grade B-cell lymphomas of mucosa-associated lymphoid tissue. We report a case of bilateral parotid lymphomas of mucosa-associated lymphoid tissue, separated diagnostically by a 13-year interval. Polymerase chain reaction analysis detected similar clones in the bilateral parotid glands. This finding supports the natural history of mucosa-associated lymphoid tissue lymphomas. In addition, because mucosa-associated lymphoid tissue lymphomas have an unpredictable period of localized disease, recognition of monoclonality in benign lymphoepithelial lesions of salivary glands is important for local cure and can be aided by combining histologic with immunohistochemical, flow cytometric immunophenotyping, and Southern blot and/or polymerase chain reaction analysis.

Aged↗
PubMed1979

Regular character of chromatin degradation in lymphoid tissues after treatment with biological alkylating agents in vivo.

The aim of the present study was to reassume the chromatin changes occurring in lymphoid tissues of mice treated with alkylating agents of the nitrogen-mustard type in relation to recent evidence on the nucleosomal organization of chromatin and to our new data on the regular character of chromatin degradation in lymphoid tissues of irradiated mice. DNA was isolated from nuclei at various intervals (1-18 h) after treatment of mice and subjected to gel electrophoresis in polyacrylamide gels. Thymus chromatin from treated mice has been shown to degrade in a regular fashion and to yield discrete DNA fragments, resembling those that originate in lymphoid tissues of irradiated mice or in thymus nuclei digested with micrococcal nuclease in vitro. With increasing interval after treatment higher amounts of smaller DNA fragments appear. Chromatin in spleen cells responds to treatment in a similar way, whilst no degradation in vivo takes place in liver chromatin. Chromatin of LS/BL lymphosarcoma cells in mice treated with alkylating agents or with irradiation suffers from a similar regular degradation. The results stress the significance of the action of liberated or activated endogenous nuclease(s) in the development of chromatin damage in lymphoid cells after treatment with alkylating agents.

Alkylating Agents↗
PubMedDate not supplied

[Effect of calcitonin on lymphoid tissue cells in vitro].

Calcitonin effect on lymphoid cells of the marrow, thymus, spleen and lymphoid nodes was studied on guinea-pigs and CBA mice. Calcitonin increased ThyI+ cell number in the marrow and thymus, restored rosette-forming ability of the thymus lymphocytes, heated at 45 degrees C within 1 hour, inducing an appearance of heteroerythrocyte receptors on their surface. The data obtained allow a conclusion that calcitonin is a substance, influencing the lymphoid tissue cell differentiation.

Animals↗
PubMed1981

Different reticular elements in rat lymphoid tissue identified by localization of Ia, Thy-1 and MRC OX 2 antigens.

An indirect immunoperoxidase method was used to localize the Ia, Thy-1 and MRC OX 2 antigens in rat lymphoid tissues. The antigens were detected using mouse monoclonal antibodies and all were notable since they were found to be expressed on different dendritic or reticular elements in lymphoid tissue. Ia antigen was present on bone marrow-derived dendritic cells in the T-dependent areas of spleen and lymph nodes in addition to B cells. MRC OX 2 antibody labelled dendritic cells in the follicles of spleen and lymph nodes but not the Ia positive cells in the T-dependent areas. Cells associated with blood vessels including the endothelium of the post capillary venules were also labelled with MRC OX 2 antibody. In contrast, anti-Thy-1 antibody labelled the pericyte sheath surrounding the post capillary venules and connective tissue elements in lymphoid tissues. The odd patterns of distribution of these antigens are discussed with respect to possible functions of the antigens and the cells they label.

Animals↗
PubMed1978

Distribution of immunoglobulin-containing cells in bone marrow and lymphoid tissues in patients with monoclonal gammapathy.

Cell suspensions of bone marrow and lymphoid tissue from 85 patients with monoclonal gammapathy were investigated by a direct immunofluorescence procedure for the detection of intracellular immunoglobulin alpha, mu, gamma, kappa and lambda chains. Serum Ig levels were determined and daily syntheric rates estimated. In all cases the majority of Ig-containing bone marrow cells contained the same Ig class as that of the M-component in serum or urine indicating a diffuse distriubtion of these clones in the bone marrow. This was observed not only in myeloma but also in benign monoclonal gammapathy (BMG) and lymphoma with an M-component. The M-component producing clone could be traced to extramedullary lymphoid tissue in myeloma but usually not in BMG. A positive correlation was found between the calculated synthetic rate of the M-component and the number of Ig-containing cells in the bone marrow and some indication was found that the synthetic rate per cell might be lower in IgM and IgG than in IgA monoclonal gammapathy. The depressed level of polyclonal Ig in myeloma and to some extent in BMG was parallelled by a diminished number of Ig-containing cells in the bone marrow.

Adult↗
PubMedDate not supplied

Mitogenic responses of the head-associated lymphoid tissues of the chicken.

A blastogenesis microassay employing 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide (MTT) was adapted to measure blastogenic responses of lymphocytes from the chicken's head-associated lymphoid tissues (i.e., the harderian gland and conjunctiva-associated lymphoid tissue) to T- and B-cell mitogens. Lymphocytes isolated from peripheral blood, spleen, and the harderian gland had highly significant (P < 0.01) responses to T- and B-cell mitogens compared with control lymphocytes cultured without mitogens. Cultured lymphocytes obtained from the harderian gland had highly significant mitogenic responses to the T-cell mitogen concanavalin A (25 to 100 micrograms/ml) and to the B-cell mitogen Salmonella typhimurium lipopolysaccharide (1.25 to 5.0 micrograms/ml) compared with the control lymphocytes. Mitogenic responses of cultured lymphocytes obtained from the conjunctiva-associated lymphoid tissue could not be measured within the given parameters of the blastogenesis microassay. This was primarily due to the low yield of lymphocytes, which proved to be a limiting factor. The ability of the MTT blastogenesis microassay to detect blastogenic responses of the harderian gland to mitogens may be indicative of its usefulness for measuring cell-mediated immunity responses to other antigens.

Animals↗
PubMed1998

Decrease of HIV-1 RNA levels in lymphoid tissue and peripheral blood during treatment with ritonavir, lamivudine and zidovudine. Ritonavir/3TC/ZDV Study Group.

OBJECTIVES: Triple combination treatment of HIV-1 infection using two reverse transcriptase inhibitors and a protease inhibitor can result in significant and sustained decreases in the quantity of viral RNA in peripheral blood. Lymphoid tissue, however, constitutes the major reservoir of HIV in infected patients. Study of the viral burden in these tissues has provided additional insight in the efficacy of antiretroviral treatment. DESIGN: Patients were randomized into two groups in order to study differences in the development of resistance to reverse transcriptase inhibitors. Group I started treatment with all three drugs simultaneously. Group II started with ritonavir monotherapy, aiming at initial reduction in virus production before the addition of lamivudine and zidovudine 3 weeks later. METHODS: Changes in the amount of HIV in plasma and tonsillar lymphoid tissue during 24 weeks of treatment with ritonavir, lamivudine and zidovudine were studied by reverse transcriptase polymerase chain reaction. RESULTS: Thirty-three antiretroviral-naive HIV-infected patients were included for analysis. After 24 weeks, median CD4+ cell count increased by 152 x 10(6)/l and median plasma viral RNA levels decreased by at least 2.87 log10 copies/ml. In 88% of the patients remaining on treatment, plasma RNA levels were below the quantification limit of the assay used (mean, 2.4 log10 copies/ml). The lymphoid tissue viral burden, ranging from 9.16 to 8.52 log10 copies/g at baseline, was markedly reduced with at least 2.1 log10 copies/g by week 24 in the five patients analysed. Eight patients (24%) withdrew because of side-effects. In one patient in group II, ritonavir and lamivudine resistance-associated mutations developed. CONCLUSIONS: Treatment with this triple antiretroviral drug combination produced a durable and strong decrease of HIV-1 RNA burden in both plasma and lymphoid tissue.

Adult↗
PubMed2006

Different T-bet expression patterns characterize particular reactive lymphoid tissue lesions.

AIMS: To investigate T-bet expression profiles in various lymphoid tissue diseases caused by intracellular pathogens and to compare them in disorders without an infective aetiology. Murine and in vitro experiments have shown that the expression/induction of T-bet, the master regulator of Th1 differentiation, can be achieved by obligate intracellular pathogens and high interferon (IFN)-gamma levels. METHODS: Lymph node biopsies were analysed immunohistochemically employing single and double labelling for T-bet and CD20, CD4, CD8 and CD30 detection. RESULTS: In disorders associated with high IFN-gamma levels and intracellular pathogens (infectious mononucleosis, HIV-associated lymphadenopathy, cat-scratch disease, and toxoplasmic lymphadenitis), T-bet-expressing CD4 cells were accompanied by significant numbers of T-bet-positive CD8 and B cells. A similar profile was also found in histiocytic necrotizing (Kikuchi) lymphadenitis, a disease of unknown cause. In contrast, T-bet expression in disorders without an infective aetiology was observed in only a small portion of lymphocytes. CONCLUSIONS: Increased T-bet expression does not only identify intracellular infections in lymphoid tissue associated with high IFN-gamma levels, but also implies that, under these conditions, it becomes induced in B cells, which apparently support the Th1 response. T-bet expression in Kikuchi lymphadenitis underscores the hypothesis that it is caused by an intracellular microorganism.

Antigens, CD20↗
PubMed2000

Human immunodeficiency virus type 1 induces apoptosis in CD4(+) but not in CD8(+) T cells in ex vivo-infected human lymphoid tissue.

Progression of human immunodeficiency virus (HIV) disease is associated with massive death of CD4(+) T cells along with death and/or dysfunction of CD8(+) T cells. In vivo, both HIV infection per se and host factors may contribute to the death and/or dysfunction of CD4(+) and CD8(+) T cells. Progression of HIV disease is often characterized by a switch from R5 to X4 HIV type 1 (HIV-1) variants. In human lymphoid tissues ex vivo, it was shown that HIV infection is sufficient for CD4(+) T-cell depletion. Here we address the question of whether infection of human lymphoid tissue ex vivo with prototypic R5 or X4 HIV variants also depletes or impairs CD8(+) T cells. We report that whereas productive infection of lymphoid tissue ex vivo with R5 and X4 HIV-1 isolates induced apoptosis in CD4(+) T cells, neither viral isolate induced apoptosis in CD8(+) T cells. Moreover, in both infected and control tissues we found similar numbers of CD8(+) T cells and similar production of cytokines by these cells in response to phorbol myristate acetate or anti-CD3-anti-CD28 stimulation. Thus, whereas HIV-1 infection per se in human lymphoid tissue is sufficient to trigger apoptosis in CD4(+) T cells, the death of CD8(+) T cells apparently requires additional factors.

Antibodies, Monoclonal↗
PubMed1980

Physicochemical characterization of the cytosol glucocorticoid receptors in various lymphoid tissues.

Cytosol glucocorticoid receptors of five different lymphoid tissues of chicken and rats were characterized and compared by physicochemical parameters. Binding specificity of receptors was found to be similar, except that cytosol receptors of chick tissues appeared slightly more specific for dexamethasone than those from rats. Association rate constants of the dexamethasone-receptor complex were higher by about one order of magnitude in the case of chicken thymus and bursa than in other cytosols. Dissociation of dexamethasone-receptor complex occurred in one step in rat tissues, whereas in case of chicken tissues two phases of dissociation were discernible. Differences between Ka and the ratio of the association and dissociation rate constants are explained by non-equilibrium conditions. The stability of receptors from the two species differed significantly, the chick receptor being more stable. Hormone-receptor complex from each tissue could be separated into two fractions by DE-52 chromatography. The peak eluted at the lower KCl concentration in the case of chick corresponded to the fast dissociating hormone-receptor complex. Kinetic analyses proved to be just as useful as ion-exchange chromatography for the characterization of, and distinguishing between, glucocorticoid receptors.

Animals↗