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Role of commensal bacteria in development of gut-associated lymphoid tissues and preimmune antibody repertoire.

Intestinal bacteria are required for development of gut-associated lymphoid tissues (GALT), which mediate a variety of host immune functions, such as mucosal immunity and oral tolerance. In rabbits, the intestinal microflora are also required for developing the preimmune Ab repertoire by promoting somatic diversification of Ig genes in B cells that have migrated to GALT. We studied the mechanism of bacteria-induced GALT development. Bacteria were introduced into rabbits in which the appendix had been rendered germfree by microsurgery (we refer to these rabbits as germfree-appendix rabbits). We then identified specific members of the intestinal flora that promote GALT development. The combination of Bacteroides fragilis and Bacillus subtilis consistently promoted GALT development and led to development of the preimmune Ab repertoire, as shown by an increase in somatic diversification of VDJ-C micro genes in appendix B cells. Neither species alone consistently induced GALT development, nor did Clostridium subterminale, Escherichia coli, or Staphylococcus epidermidis. B. fragilis, which by itself is immunogenic, did not promote GALT development; hence, GALT development in rabbits does not appear to be the result of an Ag-specific immune response. To identify bacterial pathways required for GALT development, we introduced B. fragilis along with stress-response mutants of B. subtilis into germfree-appendix rabbits. We identified two Spo0A-controlled stress responses, sporulation and secretion of the protein YqxM, which are required for GALT development. We conclude that specific members of the commensal, intestinal flora drive GALT development through a specific subset of stress responses.

Animals↗

[Comparative analysis of disorders in duodenal lymphoid tissue of mice treated with azathioprine and herbicide 2,4-dichlorophenoxyacetic acid and their correction by plant and animal origin remedies].

Comparative study of disturbances of intramural duodenal lymphoid tissue in mice, which were induced by the action of "classical" immunosuppressing drug azathioprine and by herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) showed similar immunosuppressing effect that was more potent after herbicide treatment. Significant reduction in the number of the cells of lymphoid series found in the duodenal wall was accompanied by inflammatory-destructive processes and adipose tissue outgrowth. Administration of hypolipidemic plant extract to animals immunosuppressed with either azathioprine or herbicide 2,4-D, promoted the restoration of intramural duodenal morphological structures and the restitution of lymphoid cell parameters in lamina propria practically to the level of control values. The results obtained indicate the immuno-correcting effect of the plant extract, which is determined by a rich complex of biologically active substances of its components. Active thymic fraction (AFT-2) was also found to possess an immuno-correcting effect, promoting the restoration of cellular composition of diffuse lymphoid tissue in duodenal lamina propria. Immuno-correcting effect of AFT-2 seems to result from the activity of its component thymic peptides.

2,4-Dichlorophenoxyacetic Acid↗

Organization of secondary lymphoid tissue and local IgE formation to Staphylococcus aureus enterotoxins in nasal polyp tissue.

BACKGROUND: Bilateral nasal polyposis (NP) is characterized by high concentrations of IgE in NP tissue, which show no relation to the atopic status. We aimed to study the relationship between systemic and local IgE formation, nasal carriage of Staphylococcus aureus and nasal polyposis. METHODS: In serum and nasal tissue homogenates from 24 NP patients and 12 controls, we determined concentrations of total IgE and IgE antibodies to inhalant allergens and S. aureus enterotoxins (SAEs; A,B,C,D,E,TSST) by ImmunoCAP. Tissue cryosections were stained for CD3, CD20, CD38, CD23, FcepsilonRI, IgE and SEA/SEB. RESULTS: We demonstrated a higher incidence of S. aureus colonization (17/24) and IgE antibodies to SAEs in NP tissue (12/24) compared with controls (3/12 and 0/12, respectively). Total IgE and IgE antibodies in serum and NP tissue were dissociated because of local polyclonal IgE formation in NP tissue. Staining of NP tissue revealed follicular structures characterized by B and T cells, and lymphoid accumulations with diffuse plasma cell infiltration. CONCLUSIONS: We demonstrated the organization of secondary lymphoid tissue in polyp tissue and a polyclonal hyper-immunoglobulinemia E associated with the presence of IgE antibodies to SAEs, colonization with S. aureus, and tissue eosinophilia in a relevant subgroup of polyp patients.

Adult↗

Memory T-cells in non-lymphoid tissues.

Recent studies have shown that long-lived memory CD8 T-cell populations can be subdivided into two distinct groups. The central pool of resting memory cells in lymph organs has been extensively analyzed. However, a second subset of partially activated CD8 memory T-cells has recently been identified in non-lymphoid tissues. In respiratory virus models, a strong correlation between the numbers of antigen-specific T-cells in lung tissues and effective protective cellular immunity suggests that boosting the numbers of memory T-cells in non-lymphoid tissues may be a fruitful approach in vaccine development for viral infections.

Animals↗

A case of mucosa-associated lymphoid tissue lymphoma of the parotid gland.

Non-Hodgkin's lymphomas of the salivary glands are rare. Most of these tumors occur in the parotid gland. The most common subtype is extranodal B-cell lymphoma, which arises from mucosa-associated lymphoid tissue. A 63-year-old-woman with a painless swelling in the right parotid gland was examined with magnetic resonance imaging and fine-needle aspiration cytology. The mass was excised via superficial parotidectomy. Histological examination revealed a low-grade B-cell lymphoma originating from the lymphoid tissue associated with malignant mucosa. Lymphoma should be considered in the differential diagnosis in patients having a mass in the parotid gland and a systemic or autoimmune disease.

Biopsy, Fine-Needle↗

T cells overexpressing interferon-gamma and interleukin-10 are found in both the thymus and secondary lymphoid tissues of feline immunodeficiency virus-infected cats.

Similar to human immunodeficiency virus type 1, feline immunodeficiency virus (FIV) replicates in the thymus of infected animals, causing marked alteration in thymic lymphocyte subpopulations. The immune phenotype and cytokine patterns in the thymus and secondary lymphoid tissues of FIV-infected cats were investigated. FIV infection caused an acute-stage transient reduction in CD4CD8 double-positive thymocytes, a marked increase in CD8 single-positive thymocytes, and formation of thymic B cell lymphoid follicles. Interferon (IFN)-gamma and interleukin (IL)-10 mRNA were up-regulated in both the thymus and lymph nodes of FIV-infected cats. Analysis of purified CD4 and CD8 cells revealed that CD4 cells produced most of the IL-10, whereas IFN-gamma was produced by both subsets. Quantitative-competitive reverse-transcription polymerase chain reaction analysis revealed that thymocytes, especially CD4CD8 thymocytes, had much greater levels of gag mRNA than did lymph node T cells. Thus, overexpression of IFN-gamma and IL-10 is a feature of the thymus and secondary lymphoid tissues of FIV-infected cats.

Animals↗

Nasal-associated lymphoid tissue (NALT): frequency and localization in young children.

In mucosal immunology nasal-associated lymphoid tissue (NALT) is taken as a constitutive structure of the nasal immune system and as a target tissue in strategies of local defence and an induction site for vaccination. These concepts are based on findings in rodents, but it has not been investigated systematically whether NALT also is present in humans and if so in which amount and localization. In a postmortem study the presence of NALT in humans is documented as a morphologically distinct structure additional to the lymphoid structures of the Waldeyer's ring. Human nasal tissue blocks of 150 children who had died in the first two years of life either of sudden infant death (n = 109) without signs of respiratory tract infections or of different traumatic (n = 22) and natural causes of death (n = 19) were obtained using a specific autopsy-technique and were investigated systematically using histology. Clearly in contrast to rodents human NALT was found disseminated in the nasal mucosa with typical morphological features in 38% of all children, mainly in the middle concha, with similar morphology and frequency in the examined groups. No correlation was found between the presence of NALT and the cause of death and especially the grade of inflammation in general. Therefore, NALT might be the morphological basis for inhalative vaccination strategies in young children and play a role in mucosal host defence.

Animals↗

Cyclic AMP-dependent protein kinase content of murine splenic T and B lymphocytes and non-lymphoid tissues.

Cyclic AMP-dependent protein kinase activity has been measured in DEAE-cellulose elution profiles of highly enriched murine splenic T and B Lymphocytes. B Lymphocytes were found to contain about 10% of the amount of enzyme activity associated with T lymphocytes and several non-lymphoid tissues. Cyclic AMP-independent casein kinase activities were equivalent in T and B lymphocytes. Lymphocytes contained predominantly type I isozyme as opposed to several non-lymphoid tissues which all contained predominantly the type II form.

Animals↗

[Morphology of the lymphoid tissue of the bronchus in healthy persons of various ages, and the effect of smoking].

Bronchoassociated lymphoid tissue (BALT) is studied histologically and morphometrically in 49 autopsy cases of persons of various ages after violent death. Lymphoepithelial follicles typical for BALT of small laboratory animals were not observed in human lungs of healthy persons. BALT structural components are represented by interepithelial lymphocytes, diffusely scattered lymphocytes in the mucous membrane tunica propria, lymphoid agglomerations (focal loose agglomerations in the mucous membrane tunica propria, focal periglandular and dense periductal, dense peribronchial and peribronchiolar agglomerations). According to the morphometrical study, there is BALT hyperplasia at young and adolescent ages and involutive changes at advanced age. Reduction of periglandular lymphoid agglomerations and an increase of the alveolar macrophages number were observed in adult persons who smoked for many years.

Adolescent↗

Expression of the IRTA1 receptor identifies intraepithelial and subepithelial marginal zone B cells of the mucosa-associated lymphoid tissue (MALT).

IRTA1 (immunoglobulin superfamily receptor translocation-associated 1) is a novel surface B-cell receptor related to Fc receptors, inhibitory receptor superfamily (IRS), and cell adhesion molecule (CAM) family members and we mapped for the first time its distribution in human lymphoid tissues, using newly generated specific antibodies. IRTA1 was selectively and consistently expressed by a B-cell population located underneath and within the tonsil epithelium and dome epithelium of Peyer patches (regarded as the anatomic equivalents of marginal zone). Similarly, in mucosa-associated lymphoid tissue (MALT) lymphomas IRTA1 was mainly expressed by tumor cells involved in lympho-epithelial lesions. In contrast, no or a low number of IRTA1+ cells was usually observed in the marginal zone of mesenteric lymph nodes and spleen. Interestingly, monocytoid B cells in reactive lymph nodes were strongly IRTA1+. Tonsil IRTA1+ cells expressed the memory B-cell marker CD27 but not mantle cell-, germinal center-, and plasma cell-associated molecules. Polymerase chain reaction (PCR) analysis of single tonsil IRTA1+ cells showed they represent a mixed B-cell population carrying mostly mutated, but also unmutated, IgV genes. The immunohistochemical finding in the tonsil epithelial areas of aggregates of IRTA1+ B cells closely adjacent to plasma cells surrounding small vessels suggests antigen-triggered in situ proliferation/differentiation of memory IRTA1+ cells into plasma cells. Collectively, these results suggest a role of IRTA1 in the immune function of B cells within epithelia.

Antibodies, Monoclonal↗

[Regulating role of various amino acids in development of apoptosis in organotypic culture of the nervous and lymphoid tissue].

The effect of aminoacids L-arginin, L-lysine, L-asparagin was investigated in organotypic tissue culture of brain cortex and spleen of 1-day old rats. The aminoacids in concentrations 0.05 and 0.1 ng/ml are active, inducing a less intensive growth zone as compared to the control, excluding the effect of asparagin on lymphoid tissue. Method of fluorescent staining shows a negative correlation between growth zone size and apoptotic cell number. The nerve and lymphoid tissue express apoptosis in response to aminoacids.

Amino Acids↗

Athyreotic cretinism associated with thymic hypoplasia and amyloidosis of lymphoid tissue.

A child presenting at 5 months of age with Hemophilus influenzae meningitis was also found to be severely hypothyroid. The child died two years later from the complications of measles pneumonia. At autopsy, no thyroid tissue was found and the thymus was hypoplastic. Most of the lymphoid tissues were infiltrated by amyloid.It is possible that there was a combined developmental defect involving thyroid and thymus. The alternatives are that the association occurred purely by chance or that the severe hypothyroid state led to thymic insufficiency.

Amyloidosis↗

Decreased human immunodeficiency virus type 1 plasma viremia during antiretroviral therapy reflects downregulation of viral replication in lymphoid tissue.

Although several immunologic and virologic markers measured in peripheral blood are useful for predicting accelerated progression of human immunodeficiency virus (HIV) disease, their validity for evaluating the response to antiretroviral therapy and their ability to accurately reflect changes in lymphoid organs remain unclear. In the present study, changes in certain virologic markers have been analyzed in peripheral blood and lymphoid tissue during antiretroviral therapy. Sixteen HIV-infected individuals who were receiving antiretroviral therapy with zidovudine for > or = 6 months were randomly assigned either to continue on zidovudine alone or to add didanosine for 8 weeks. Lymph node biopsies were performed at baseline and after 8 weeks. Viral burden (i.e., HIV DNA copies per 10(6) mononuclear cells) and virus replication in mononuclear cells isolated from peripheral blood and lymph node and plasma viremia were determined by semiquantitative polymerase chain reaction assays. Virologic and immunologic markers remained unchanged in peripheral blood and lymph node of patients who continued on zidovudine alone. In contrast, a decrease in virus replication in lymph nodes was observed in four of six patients who added didanosine to their regimen, and this was associated with a decrease in plasma viremia. These results indicate that decreases in plasma viremia detected during antiretroviral therapy reflect downregulation of virus replication in lymphoid tissue.

Adult↗

The detection of mature T- and B-cells during development of the lymphoid tissues of the tammar wallaby (Macropus eugenii).

The distribution of T- and B-cells in the developing lymphoid and immunohaematopoietic tissues of the tammar wallaby were investigated using antibodies to the mature cell surface markers, CD3, CD5 and CD79b. In the thymus, CD3- and CD5-positive T-cells were first observed at day 12 postpartum whilst rare B-cells were first detected at day 23. Both T- and B-lymphocytes were first stained on day 21 postpartum in the spleen and day 24 in lymph nodes. In one sample from a 7-day-old animal, rare CD79b-positive (CD79b+) lymphocytes were observed in the gut-associated lymphoid tissues. However, CD3+ cells were not apparent until day 12 and CD5+ cells were not detected until day 74 postpartum. No lymphocytes were detected in liver or bone marrow samples and no bronchus-associated lymphoid tissues were observed. The pattern of development and the distribution of T- and B-cells in the lymphoid and immunohaematopoietic tissues were similar to those observed in eutherian mammals and in limited studies of other metatherians. However, the detection of apparently mature T- and B-cells in the thymus and gut-associated lymphoid tissues (GALT) at the same postnatal age highlights the need for a more substantial study of the development of GALT. This is, at present, limited by availability of marsupial-specific antibodies.

Animals↗

Distribution of T and B lymphocytes in blood and lymphoid tissues of fetal and adult sleep.

Distributions of B and T lymphocytes in blood and various lymphoid tissues of clinically normal adult and fetal sheep were studied. The B and T lymphocytes were identified in enriched preparations of blood lymphocytes and cell suspensions of solid tissues. The T lymphocytes were quantitated by indirect immunofluorescence, using rabbit antisera to sheep thymus cells. The B lymphocytes were identified by direct immunofluorescence, using rabbit antisera to sheep immunoglobulin.

Animals↗

Expression of IFI 16 in epithelial cells and lymphoid tissues.

IFI 16 is a member of the HIN-200 protein family named for their haemopoietic expression, interferon-inducibility and nuclear localisation. These proteins have been characterised as transcriptional regulators that modulate the cell cycle. IFI 16 is expressed in some haemopoietic lineages including CD34+ progenitor cells, mature lymphocytes and monocytes, but is absent from granulocytes, erythrocytes and megakaryocytes. We present a wider study of IFI 16 expression in normal human tissues using a monoclonal antibody specifically recognising the C-terminus of IFI 16. As expected, IFI 16 was detected in the nuclei of lymphocytes in the spleen, thymus, lymph node and palatine tonsil, but was also found in epithelial cells in these tissues. Interestingly, IFI 16 protein was also expressed in non-lymphoid tissues including trachea, gastrointestinal tract, skin and testis, but was absent from others including heart and brain. In each tissue, IFI 16 was predominantly expressed in surface epithelial cells and staining was strongest in basal epithelial layers. Therefore, IFI 16 expression is not restricted to cells of the immune system, but is also expressed in epithelial cells. In contrast to the perceived role of HIN-200 proteins as suppressors of cell growth, maximal expression of IFI 16 was in cells with high proliferative potential.

Antibodies, Monoclonal↗

Lymphoma of mucosa-associated lymphoid tissue in common variable immunodeficiency.

Common variable immunodeficiency (CVID) is the most common symptomatic primary immunodeficiency characterized by reduced levels of all major immunoglobuline classes and recurrent c infections. The risk of non-Hodgkin's lymphoma (NHL) among patients with CVID was found to be increased in different studies. Mucosa-associated lymphoid tissue (MALT) lymphomas are a recently recognized sub-set of low-grade B-cell NHL composed of marginal zone-related cells. MALT lymphomas appear in the lymphoid tissues as a result of chronic inflammatory or autoimmune stimulation. This study briefly reviews previously published cases and reports a patient suffering from CVID with a history of chronic diarrhea and recurrent sinopulmonary infections. Despite treatment with intravenous immunoglobulin, chronic cough and wheezing progressed. Open lung biopsy showed a MALT lymphoma. Although a rare complication, pulmonary low grade B-cell lymphoma is a diagnosis that must be kept in mind in CVID patients with chronic pulmonary symptoms unresponsive to conventional therapies.

Adolescent↗

Immunolocalization of integrin receptors in normal lymphoid tissues.

The integrin superfamily of cell adhesion receptors consists of heterodimeric glycoproteins composed of unique alpha and beta subunits. These receptors mediate cell-substrate and cell-cell adhesive properties for a variety of cell types. This investigation has focused on the histologic distribution of the beta 1 subfamily of integrins within lymphoid tissues including tonsil, lymph node, spleen, thymus, and appendix. The dendritic cells of both follicular center and thymic origin express the alpha 1, alpha 2, alpha 3, alpha 5, and alpha 6, as well as the beta 1 integrin subunits. Most lymphoid cells in normal tissues do not express the alpha 1, alpha 2, alpha 3, alpha 5, and alpha 6 subunits, or the alpha v beta 3 integrin. The beta 1 subunit is expressed by all lymphocytes but with variable intensity. Increased levels of the alpha 5 and beta 1 subunits are observed in the follicular light zone, suggesting a role for these integrins in B-cell activation. Although the alpha 4 subunit is expressed by all lymphoid cells, an increased expression of alpha 4 and decreased expression of beta 1 by the mantle zone B-cell compartment is noted in comparison with the decreased expression of alpha 4 and increased expression of beta 1 by follicular center B-cells. These studies suggest that alpha 4 may be paired with a beta subunit other than beta 1 on the mantle zone lymphoid population. Thus, integrin expression by cells of lymphoid tissues varies with location and function and differs significantly from integrin expression observed on circulating and cultured peripheral blood lymphocytes.

Appendix↗