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PubMed1990

Lymphoid and non-lymphoid cells in nasal-associated lymphoid tissue (NALT) in the rat. An immuno- and enzyme-histochemical study.

Lymphocyte and macrophage subpopulations and the stroma of mucosa-associated lymphoid tissue in the nasal cavity of the rat were examined by application of immunohistochemical and enzyme histochemical methods to cryostat sections. Nasal-associated lymphoid tissue was composed of a loose reticular network with lymphocytes and macrophages, covered by epithelium. The epithelium was infiltrated with B cells. T helper (W3/13-positive) and T suppressor/cytotoxic or large granular cells (OX8-positive), ED1-positive macrophages and Ia-positive cells. The B cell areas were populated by B cells, immunopositive for surface IgM or IgG. B cells with surface IgA or IgE were rare. Germinal centres were found infrequently. T helper cells were scattered throughout the B cell area. A few ED1-positive macrophages and ED5-positive follicular dendritic cells were observed. Strong Ia staining (mostly of B cells) was found in this area. The T cell areas contained T helper and T suppressor/cytotoxic cells in about equal amounts, and numerous ED1-positive macrophages. ED1 staining was also found in the subepithelial area. Numerous ED1-, ED2- and ED3-positive macrophages were found in the border between the lymphoid mass and the surrounding connective tissue. A few non-lymphoid cells showed weak acid phosphatase or non-specific esterase activity. The morphological observations suggest that nasal-associated lymphoid tissue plays an important role in the first contact with inhaled antigens.

Animals↗
PubMed2006

Rapid dissemination of a pathogenic simian/human immunodeficiency virus to systemic organs and active replication in lymphoid tissues following intrarectal infection.

A better understanding of virological events during the early phase of human immunodeficiency virus 1 (HIV-1) infection is important for development of effective antiviral vaccines. In this study, by using quantitative PCR and an infectious plaque assay, virus distribution and replication were examined in various internal organs of rhesus macaques for almost 1 month after intrarectal inoculation of a pathogenic simian immunodeficiency virus/HIV chimeric virus (SHIV-C2/1-KS661c). At 3 days post-inoculation (p.i.), proviral DNA was detected in the rectum, thymus and axillary lymph node. In lymphoid tissues, infectious virus was first detected at 6 days p.i. and a high level of proviral DNA and infectious virus were both detected at 13 days p.i. By 27 days p.i., levels of infectious virus decreased dramatically, although proviral DNA load remained unaltered. In the intestinal tract, levels of infectious virus detected were much lower than in lymphoid tissues, whereas proviral DNA was detected at the same level as in lymphoid tissues throughout the infection. In the thymus and jejunum, CD4CD8 double-positive T cells were depleted earlier than CD4 single-positive cells. These results show that the virus spread quickly to systemic tissues after mucosal transmission. Thereafter, infectious virus was actively produced in the lymphoid tissues, but levels decreased significantly after the peak of viraemia. In contrast, in the intestinal tract, infectious virus was produced at low levels from the beginning of infection. Moreover, virus pathogenesis differed in CD4 single-positive and CD4CD8 double-positive T cells.

Animals↗
PubMed1984

Natural killer (Leu 7+) cells in reactive lymphoid tissues and malignant lymphomas.

Leu 7 (HNK-1) is a monoclonal antibody reported to identify human natural killer/killer cells. The frequency and distribution of Leu 7+ cells in 14 reactive lymphoid tissues and 47 malignant lymphomas were studied using the frozen section immunoperoxidase technic. In reactive lymphoid tissues, Leu 7+ cells were concentrated in the pale zone of germinal centers and usually were relatively scarce in the interfollicular areas. Of the malignant lymphomas, follicular lymphomas most consistently had numerous admixed Leu 7+ cells and lymphoblastic lymphomas the least. The authors' findings suggest that Leu 7+ cell accumulation in normal and neoplastic lymphoid tissue is associated at least in part with something shared by the pale zone of the normal germinal centers and the presence of neoplastic germinal centers. This association does not appear to be a simple response to lymphoid proliferation.

Antibodies, Monoclonal↗
PubMed1998

Secondary lymphoid-tissue chemokine is a functional ligand for the CC chemokine receptor CCR7.

Secondary Lymphoid-tissue Chemokine (SLC) is a recently identified CC chemokine that is constitutively expressed in various lymphoid tissues and is a potent and specific chemoattractant for lymphocytes. The SLC gene and the gene encoding another lymphocyte-specific CC chemokine, EBI1-ligand chemokine (ELC), form a mini-cluster at human chromosome 9p13. Here, we show that SLC is a high affinity functional ligand for chemokine receptor 7 (CCR7) that is expressed on T and B lymphocytes and a known receptor for ELC. SLC induced a vigorous calcium mobilization in murine L1.2 cells stably expressing human CCR7. SLC tagged with the secreted form of alkaline phosphatase (SLC-SEAP) showed specific binding to CCR7 that was fully competed by SLC with an IC50 of 0.5 nM. SLC also induced a vigorous chemotactic response in CCR7-expressing L1.2 cells with a typical bell-shaped dose-response curve and a maximal migration at 10 nM. When assessed using CCR7-transfected L1.2 cells, SLC and ELC were essentially equivalent in terms of cross desensitization in calcium mobilization via CCR7, cross-competition in binding to CCR7, and induction of chemotaxis via CCR7. SLC and ELC were also shown to fully share receptors expressed on cultured normal T cells known to express CCR7. Notably, however, SLC was somehow less efficient in cross-desensitization against ELC in calcium mobilization and in cross-competition with ELC for binding when assessed using cultured normal T cells. Thus, SLC and ELC, even though sharing only 32% amino acid identity, constitute a genetically and functionally highly related subgroup of CC chemokines.

Amino Acid Sequence↗
PubMed2000

Whole body positron emission tomography imaging of activated lymphoid tissues during acute simian-human immunodeficiency virus 89.6PD infection in rhesus macaques.

Mechanisms of acute retroviral pathogenesis have been examined during primary infection of rhesus macaques with simian-human immunodeficiency virus 89.6PD (SHIV(89.6PD)). During acute infection, between initial exposure and establishment of antigen-specific immune responses that stabilize the virus burden, rapid immune system changes influence the viral set-point and dictate subsequent steps in disease progression. In a previous study, we described specific patterns of lymphocyte activation during acute SHIV(89.6PD) infection. We now extend these studies to describe lymphoid tissue activation, using whole body positron emission tomography (PET) and the radioactive tracer 2-[(18)F]fluorodeoxyglucose (FDG). Within a few days after primary infection by intravenous, intrarectal, or intravaginal routes, PET-FDG imaging revealed a distinct pattern of lymphoid tissue activation centered on axillary, cervical, and mediastinum lymph nodes. Increased tissue FDG uptake preceded fulminant virus replication at these sites, suggesting that a diffusible factor of host or viral origin was responsible for lymphoid tissue changes. These data show that activation of lymphoid tissues in the upper body is an early response to virus infection and that diffusible mediators of activation might be important targets for vaccine or therapeutic intervention strategies.

Acute Disease↗
PubMedDate not supplied

Structure and development of bronchus-associated lymphoid tissue in conventionally reared broiler chickens.

The development of bronchus-associated lymphoid tissue (BALT) in conventionally reared broiler chickens of 1 day and 1, 2, 3, 4, 6, and 8 weeks of age was studied using light and electron microscopy (scanning and transmission). BALT in these chickens resembled other mucosa-associated lymphoid tissues (MALT) in that it was composed of an altered epithelium overlying a population of lymphocytes and contained potential antigen-presenting cells, such as macrophages and dendritic cells; high endothelial venules were also present. In contrast to other MALT, epithelial cells in chicken BALT were not of the M-cell type; i.e., they lacked large numbers of apical tubules and vesicles for specialized uptake of luminal antigens. There were age-related differences in size, number, and cellular composition of BALT nodules. Lymphoid nodules were progressively larger and more numerous with increasing age. Germinal centers were present in birds 2 weeks of age and older. BALT epithelium was primarily squamous and non-ciliated in 1-day and 1-week-old chicks, becoming progressively more columnar and ciliated in older chickens. Lymphocyte infiltration of the epithelium was extensive at 1 to 4 weeks of age; in older chickens, distinct epithelial and lymphocytic compartments were separated by connective tissue.

Animals↗
PubMed2006

Type I interferon production by tertiary lymphoid tissue developing in response to 2,6,10,14-tetramethyl-pentadecane (pristane).

Lymphoid neogenesis is associated with antibody-mediated autoimmune diseases such as Sjogren's syndrome and rheumatoid arthritis. Although systemic lupus erythematosus is the prototypical B-cell-mediated autoimmune disease, the role of lymphoid neogenesis in its pathogenesis is unknown. Intraperitoneal injection of 2,6,10,14-tetramethyl-pentadecane (TMPD, pristane) or mineral oil causes lipogranuloma formation in mice, but only TMPD-treated mice develop lupus. We report that lipogranulomas are a form of lymphoid neogenesis. Immunoperoxidase staining of lipogranulomas revealed B cells, CD4(+) T cells, and dendritic cells and in some cases organization into T- and B-cell zones. Lipogranulomas also expressed the lymphoid chemokines CCL21, CCL19, CXCL13, CXCL12, and CCL22. Expression of the type I interferon (IFN-I)-inducible genes Mx1, IRF7, IP-10, and ISG-15 was greatly increased in TMPD- versus mineral oil-induced lipogranulomas. Dendritic cells from TMPD lipogranulomas underwent activation/maturation with high CD86 and interleukin-12 expression. Magnetic bead depletion of dendritic cells markedly diminished IFN-inducible gene (Mx1) expression. We conclude that TMPD-induced lupus is associated with the formation of ectopic lymphoid tissue containing activated dendritic cells producing IFN-I and interleukin-12. In view of the increased IFN-I production in systemic lupus erythematosus, these studies suggest that IFN-I from ectopic lymphoid tissue could play a role in the pathogenesis of experimental lupus in mice.

Animals↗
PubMed1991

Intestinal mucosa and intra-abdominal lymphoid tissues of the platypus, Ornithorhynchus anatinus.

The morphological features of the intestinal mucosa and intra-abdominal lymphoid tissues of the platypus were examined. The mucosal surface of the intestine was characterized by the formation of large folds instead of the finger-like villi found in placental mammals. The lamina propria of the mucosal fold was well developed and contained numerous lymphocytes, expressing the lymphoid nature which is characteristic of the lamina propria of mammalian intestines. Although numerous well-developed Peyer's patches were observed in the ileum, solitary lymphoid nodules could not be found anywhere in the small intestine. Other intra-abdominal lymphoid tissues, particularly mesenteric lymphoid nodules, were well developed. However, each nodule represented a single follicle in contrast to the mammalian mesenteric lymph node which is composed of numerous follicles fused together. On the basis of the above findings, the tissues in question are considered to be at an evolutionary level preceding that of placental mammals.

Abdomen↗
PubMed1996

Cellular distribution of bronchus-associated lymphoid tissue in rheumatoid arthritis.

Bronchus-associated Lymphoid tissue (BALT) has been reported to be present in the lungs of patients with rheumatoid arthritis (RA). However, little is known about the structure and cellular distribution of BALT in this disease, so we investigated these points using immunohistochemical methods. The subjects were eight RA patients with BALT in biopsy specimens and a histologic diagnosis of follicular bronchiolitis. Seven patients had cough and purulent sputum, and four patients had positive sputum cultures. BALT was histologically composed of four distinct regions, which were the lymphoepithelium, the dome area, the follicular area, and the parafollicular area. Surface IgM+ B cells were predominant in the follicular area, whereas IgA+ cells were scattered in the dome and parafollicular areas. T cells were mainly found in the parafollicular area (CD4+ > CD8+), and most of them expressed the T Cell receptor alpha beta (alpha beta TCR). These findings were similar to those described previously for BALT in diffuse panbronchiolitis, which manifests as a chronic respiratory infection. The present study indicated that extrinsic stimulation as well as alterations of the immune response are involved in the development of BALT in RA, although the exact mechanism requires further clarification.

Adult↗
PubMed1998

Myelin protein expression in lymphoid tissues: implications for peripheral tolerance.

During chronic relapsing experimental autoimmune encephalomyelitis (EAE), T lymphocytes specific for myelin protein epitopes are stimulated in vivo. When epitopes are unique from the disease-initiating myelin protein epitope, this phenomenon has been termed "epitope spreading". These T-lymphocyte responses have been detected primarily in lymph node and spleen during the relapsing phase of disease. If myelin proteins are sequestered behind the blood brain barrier, a fundamental question arises: where does the in vivo stimulation of T lymphocytes occur during relapsing EAE? While it has been thought that epitope spreading may occur within the central nervous system (CNS), here we present data supporting a novel hypothesis. Epitope spreading during EAE may not occur within the CNS, but rather within lymphoid tissues. Both myelin basic protein (MBP) and proteolipid protein (PLP) are expressed at the RNA and protein level in lymph node, thymus and spleen of SJL mice with relapsing EAE. This myelin protein expression occurs within T lymphocytes, B lymphocytes and macrophages. Further, T-lymphocyte lines from SJL mice specific for the immunodominant and subdominant epitopes of MBP and PLP can recognize endogenous protein within cells derived from lymphoid tissues. Thus, immunologically relevant myelin proteins are endogenously produced and presented within lymphoid tissues. The hypothesis that epitope spreading occurs within lymphoid tissues would explain how myelin protein-specific T lymphocytes become activated outside the CNS to allow their passage through the blood brain barrier to form new CNS lesions during relapses.

Animals↗
PubMed1988

Secretory immune responses in ageing rats. II. Phenotype distribution of lymphocytes in secretory and lymphoid tissues.

The distribution of lymphocyte phenotypes was examined in various tissues from weanling (21-35 days), adult (3-4 months), mid-life (10-12 months) and senescent (18-20 months) rats. Lymphoid tissues included peripheral blood, spleen, cervical, mesenteric and inguinal lymph nodes. Tissues associated with secretory immune responses were also examined, including submandibular and parotid salivary glands, extraorbital lacrimal glands and Peyer's patches. IgA, IgG and IgM B cells were determined by surface Ig staining. Total T cells (W3/13), T helper/inducer (Th) (W3/25), T suppressor/cytotoxic (Ts) (OX8) and immature T cells (Thy 1.1; OX7) were also evaluated. IgG B cells were significantly decreased in lymphoid tissues from the senescent rats, while the weanling group exhibited decreased levels of all three B-cell isotypes compared to adult animals. IgA B cells were significantly decreased in the secretory tissues of the senescent rats, while IgM B cells were increased in both the weanling and senescent groups. Total T-cell percentages were unaffected by ageing in any of the tissues. The only consistent alteration in the lymphoid tissues was a decrease in Thy 1.1-positive cells in the older groups compared to the weanling group. A decreased Th cell percentage was demonstrated in the salivary and lacrimal glands of the weanling and senescent groups. Decreases in Th/Ts ratios, as well as decreased numbers of plasma cell precursors in the secretory tissues of the aged rats, suggests that alterations in normal secretory immune responses may be expected to accompany the ageing process.

Aging↗
PubMed2000

Lymphoid tissue homing chemokines are expressed in chronic inflammation.

Secondary lymphoid tissue chemokine (SLC) and B lymphocyte chemoattractant (BLC) are homing chemokines that have been implicated in the trafficking of lymphocytes and dendritic cells in lymphoid organs. Lymphotoxin-alpha (LTalpha), a cytokine crucial for development of lymphoid organs, is important for expression of SLC and BLC in secondary lymphoid organs during development. Here we report that transgenic expression of LTalpha induces inflammation and ectopic expression of SLC and BLC in the adult animal. LTbeta was not necessary for induction of BLC and SLC in inflamed tissues, whereas, in contrast, tumor necrosis factor receptor-1 was found to be important for the LTalpha-mediated induction of these chemokines. The ectopic expression of LTalpha is associated with a chronic inflammation that closely resembles organized lymphoid tissue and this lymphoid neogenesis can also be seen in several chronic inflammatory diseases, including in the pancreas of the prediabetic nonobese diabetic (NOD) mouse. Expression of SLC was also observed in the pancreas of prediabetic NOD mice. This study implicates BLC and SLC in chronic inflammation and presents further evidence that LTalpha orchestrates lymphoid organogenesis both during development and in inflammatory processes.

Animals↗
PubMed2002

Changes in distribution and numbers of CD4+ and CD8+ T-lymphocytes in lymphoid tissues and intestinal mucosa in the early phase of experimentally induced early onset mucosal disease in cattle.

Mucosal disease (MD), one sequelae of bovine virus diarrhoea virus (BVDV) infection, causes severe lesions in lymphoid tissues and mucosal surfaces. Lesions are associated with the presence of cytopathogenic (cp) BVDV and initially characterized by apoptotic cell death. The objective of this investigation was to determine if this cell death is mediated only by the cp BVDV, which is known to induce apoptosis in cell culture or if immune-mediated host reactions might also contribute. Early onset MD was experimentally induced in calves by inoculation of persistently viremic calves with a closely related cp BVDV. Calves were euthanized in the early phase of infection between days 5 and 13 post-inoculation and tissues from tonsils, lymph nodes, Peyer's patches, jejunum and colon were collected. Presence of cp BVDV antigen was correlated with distribution of lymphocyte subpopulations in consecutive cryostat sections. In the lymphoid tissues, cp BVDV antigen was predominantly found in the lymphoid follicles. The increase of infected cells with time post-inoculation was paralleled by a decrease of B-lymphocytes and an increase of CD4+ T-lymphocytes. An increased number of CD8+ T-lymphocytes was seen in progressed lesions only. In the intestinal mucosa, initially multifocal, later diffuse infection with cp BVDV was accompanied by a multifocal or diffuse increase of CD4+ T-lymphocytes, respectively. Numbers of IgA+ plasma cells and CD8+ T-lymphocytes were decreased. The common change observed in lymphoid tissues and mucosa was the increase of CD4+ T-lymphocytes in sites with lesions. This might indicate a cell-mediated immune response to the cp BVDV. Besides their helper function to other cells of the immune system, activated CD4+ T-lymphocytes might also exert cytotoxic activity, induce apoptosis in target cells via Fas/Fas ligand binding and thus contribute to the severity of tissue lesions in MD.

Animals↗
PubMed1988

Lymphoid tissue responses to emulsified perfluorochemicals: comparative aspects.

The effects of a single, low dose (10 ml/kg) injection of the perfluorochemical (PFC) emulsion, Fluosol-DA 20%, on lymphoid tissues and antibody production against sheep red blood cells (SRBC) have been studied relative to the timing of immunization in rats and mice. Intravenous (i.v.) or intraperitoneal (i.p.) injection of emulsion in both species produced alterations in lymphoid tissue weights and the magnitude of these responses was highly tissue- and species-specific. Injection of Fluosol-DA tended to potentiate the humoral immune response to SRBC but this depended on timing and route of emulsion administration relative to immunization. We conclude that lymphoid tissue responses to emulsified PFCs are highly variable and depend upon a number of factors including: emulsion composition and dose; route and timing of administration relative to immunological "challenge"; tissue and species examined.

Animals↗
PubMed2003

L-Selectin ligands in lymphoid tissues and models of inflammation.

Both lymphocyte recirculation through the lymphoid tissues and leukocyte recruitment to sites of inflammation are essential components of immune surveillance, and are necessary for sustained protection against pathogens. This process is mediated by the leukocyte-endothelial adhesion cascade of which the interaction of leukocyte L-Selectin with its endothelial ligand initiates the first critical tethering and rolling step. As well as discussing the constitutive L-Selectin ligands in lymphoid tissues, this review examines the literature regarding their induction in inflammation, and draws attention to recent findings regarding soluble L-Selectin ligands that suggest an emerging multifunctional role in leukocyte recirculation and inflammation.

Animals↗
PubMed1995

[A morphological study of lymphocyte homing in conjunctiva-associated lymphoid tissue].

High endothelial venule (HEV) is an important component of the mucosa-associated lymphoid tissue and plays a role in the homing phenomenon of lymphocytes. We investigated the presence of HEVs in conjunctiva-associated lymphoid tissue (CALT) using guinea pigs sensitized with ovalbumin. Electron microscopy showed characteristic findings for HEVs in the parafollicular area of the CALT. Lymphocytes in the vessels are trapped not only by microprocesses extending from the vascular endothelium but also by the endothelial cells. Some endothelial cells also appear to release lymphocytes. We conclude that HEVs are present also in the CALT.

Animals↗
PubMed1999

Systemic antibodies can inhibit mouse mammary tumor virus-driven superantigen response in mucosa-associated lymphoid tissues.

Many mucosal pathogens invade the host by initially infecting the organized mucosa-associated lymphoid tissue (o-MALT) such as Peyer's patches or nasal cavity-associated lymphoid tissue (NALT) before spreading systemically. There is no clear demonstration that serum antibodies can prevent infections in o-MALT. We have tested this possibility by using the mouse mammary tumor virus (MMTV) as a model system. In peripheral lymph nodes or in Peyer's patches or NALT, MMTV initially infects B lymphocytes, which as a consequence express a superantigen (SAg) activity. The SAg molecule induces the local activation of a subset of T cells within 6 days after MMTV infection. We report that similar levels of anti-SAg antibody (immunoglobulin G) in serum were potent inhibitors of the SAg-induced T-cell response both in peripheral lymph nodes and in Peyer's patches or NALT. This result clearly demonstrates that systemic antibodies can gain access to Peyer's patches or NALT.

Animals↗
PubMed1984

Interdigitating cells in the lymphoid tissues of bovine fetuses and calves. An electron-microscopic study.

Electron-microscopic studies of lymphoid tissues from bovine fetuses and from calves disclosed a non-lymphoid cell type in the thymus-dependent zones of secondary lymphoid tissues and in the thymus that is distinguishable from reticulum cells, epithelial and endothelial cells, and macrophages. Based on morphological and topographical criteria, the cell is identified as the interdigitating cell. In addition, studies of the tissues of normal and virus-challenged fetuses, and of conventionally reared calves, indicated that the interdigitating cells originate from monocytoid cells, which undergo differentiation in the thymus-dependent zones during an immune response.

Animals↗