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PubMed1987

Flow cytometric analysis of DNA in cells obtained from deparaffinized formalin-fixed lymphoid tissues.

Flow cytometric analysis of DNA content was performed on nuclear suspensions prepared from fresh and from paraffin-embedded, formalin-fixed lymphoid tissues. We confirmed previous reports that it is possible to obtain nuclear suspensions from deparaffinized, formalin-fixed tissues, suitable for DNA analysis by flow cytometry. We observed a tendency for a larger coefficient of variation (CV) of the DNA measurements in the fixed tissues than in the unfixed material causing abnormalities in 2 of 19 lymphomas to become undetectable. Furthermore, samples from different paraffin blocks of a single tumor with an extra G1 (hyperdiploid) peak showed marked differences in the CV of the hyperdiploid peak while the CV of the diploid peak was similar in all samples. In both benign and malignant lymphoid tissues, the S-phase fraction was higher in paraffin-embedded tissues than in unfixed cells. This difference could be attributed to 4', 6'-diamidino-2-phenylindole dihydrochloride (DAPI), a DNA-binding dye commonly used in this technique. Nevertheless, intermediate and high grade lymphomas from paraffin-embedded tissues generally showed a greater S-fraction than low grade lymphomas, a similar observation as with unfixed tissues. Therefore, DNA content analysis of nuclei extracted from paraffin sections may be inadequate to resolve slight aneuploidy, but the measurement of S-fraction size may remain diagnostically or prognostically valuable. Large retrospective studies will be necessary to determine the clinical impact of this technique in the analysis of lymphomas.

Cell Nucleus↗
PubMed1987

Seasonal involution of gut-associated lymphoid tissue of the European ground squirrel.

Small intestine-associated lymphoid tissue of immature, male ground squirrels of the genus Citellus citellus L. was studied histologically throughout the annual cycle. Circannual morphological changes of the lymphoid cells in the lamina propria of the mucosa as well as of the Peyer's patches in the submucosa, were established. The changes consisted mainly in a gradual decrease in the proliferative activity of the cells in the autumn and in arrest of this activity in hibernating animals during the first phase of hibernation. An involution of the follicles and their germinative centres, as well as lymphocyte depletion in the Peyer's patche parenchyma, and a marked increase in the lymphocyte number of the lamina propria in hibernating ground squirrels were found. It was shown that the activation of the lymphoid cell proliferation in both compartments of the small intestine begins in hibernating animals in January.

Acclimatization↗
PubMed1996

Molecular cloning of TER1, a chemokine receptor-like gene expressed by lymphoid tissues.

Several chemokine receptors have been cloned and shown to belong to a superfamily of seven transmembrane, G protein-coupled receptors. We report here the molecular cloning of TER1, a novel human chemokine receptor-like gene. The amino acid sequence deduced from the TER1 cDNA shows 43, 40, 40, and 39% identity to CCR4, CCR5, CCR1, and CCR2B beta chemokine receptors, respectively. By the use of fluorescent in situ hybridization, we have mapped the TER1 gene to chromosome 3p21, clustered with other chemokine receptor genes. By Northern blot analysis, TER1 mRNA is found to be expressed in the thymus, spleen, and at barely detectable levels in peripheral blood lymphocytes. Moreover, TER1 message in abundant in the NK cell line NK3.3 and in the T cell line MOLT-4. The restricted TER1 expression in cells and tissues of the lymphoid lineage suggests that this receptor may play a role in regulating immune functions.

Amino Acid Sequence↗
PubMed2006

Abnormal prion protein in ectopic lymphoid tissue in a kidney of an asymptomatic white-tailed deer experimentally inoculated with the agent of chronic wasting disease.

Chronic wasting disease (CWD), a transmissible spongiform encephalopathy (TSE) of deer and elk, is one of a group of fatal, neurologic diseases that affect several mammalian species, including human beings. Infection by the causative agent induces accumulations of an abnormal form of prion protein (PrPres) in nervous and lymphoid tissues. This report documents the presence of PrPres within ectopic lymphoid follicles in a kidney of a white-tailed deer that had been experimentally inoculated by the intracerebral route with CWD 10 months previously. The deer was nonclinical, but spongiform lesions characteristic of TSE were detected in tissues of the central nervous system (CNS) and PrPres was seen in CNS and in lymphoid tissues by immunohistochemistry. The demonstration of PrPres in lymphoid tissue in the kidney of this deer corroborates a recently published finding of PrPres in lymphoid follicles of organs other than CNS and lymphoid tissues in laboratory animals with TSE (scrapie).

Animals↗
PubMed2000

Antibody repertoire development in fetal and newborn piglets, III. Colonization of the gastrointestinal tract selectively diversifies the preimmune repertoire in mucosal lymphoid tissues.

Changes in the VH-region repertoire of isolator piglets reared for 6 weeks under germ-free (GF) conditions and those colonized (COL) with a defined exclusion flora on the 1st day of life were compared. Although serum immunoglobulin levels were 20-100-fold higher in COL piglets than GF piglets, an analysis of peripheral blood B cells (PBBs) indicated that: GF and COL piglets used the same four VH genes and two DH segments during the 6-week period; proportional usage of VH genes and DH segments was the same as in fetal animals; and VH and DH usage did not differ between COL and GF animals. This pattern differed from the PBBs from 6-week-old conventional (CONV) piglets. When the sequences of 73 splenic CDR3 segments were analysed, DH usage and mutation frequency were the same in sequences from both 6-week-old GF and COL piglets; mutations were infrequent and occurred with the same frequency as in 110-day fetal spleen. However, the median CDR3 length in COL piglets was shifted upward due to 3' DH N-nucleotide additions. Neither COL nor GF animals made specific serum antibodies to phosphoryl choline given parenterally on a T-cell dependent carrier. In contrast to the near absence of a colonization effect in PBBs and splenic DNA, rearranged variable heavy-chain gene segments (VDJs) recovered from the DNA of mucosal lymphoid tissues of COL piglets showed pronounced differences from those recovered from GF animals in usage of DHA-, DHB-and VHB- and in the frequency of point mutation. The mucosal VDJ transcripts and those from the spleen were similarly affected by colonization. This effect on mucosal lymphoid tissue was consistent with the five-fold selective increase in serum immunoglobulin A (IgA) levels relative to IgM and IgG. Comparison of IgM and IgA transcripts from mucosal tissues suggested that IgA and IgM clones diversify in parallel. Our findings are the first to show that colonization of the gastrointestinal tract of offspring separated from their mothers, differs from 'conventionalized' GF animals in that colonization preferentially influences diversification and expansion of the preimmune IgM and IgA repertoire in mucosal lymphoid tissues but not in PBBs and seldom/modestly in VDJs from splenic DNA.

ATP-Binding Cassette Transporters↗
PubMed2000

Immunocytochemical detection of Ig-positive cells in blood, lymphoid organs and the gut associated lymphoid tissue of the turbot (Scophthalmus maximus).

The present study was designed to search for the sites of the B-cell lineage in the different lymphoid organs of turbot (Scophthalmus maximus) by immunoperoxidase staining with a rabbit polyclonal antiserum against deglycosylated turbot IgM (TUDG-6). A turbot immunoglobulin (Ig) fraction, isolated by protein A, was checked for purity by gel filtration and SDS-PAGE under reducing conditions. The turbot IgM was deglycosylated and used to raise an antiserum. The antiserum titre was evaluated in ELISA. It was then used to analyse turbot peripheral blood leucocytes for membrane and cytoplasmic Ig and for immunohistochemistry with turbot lymphoid tissues. Very low numbers of Ig+ cells were found in thymus sections. In sections of spleen, Ig+ cells were observed in white pulp, around ellipsoids but were mostly concentrated and associated with melanomacrophage centers (MMCs). The lymphoid Ig+ cells in the kidney tended to be dispersed among haematopoietic and granulopoietic cell populations and were in intimate association with the MMCs and blood vessels. This association between MMCs and Ig+ cells in the spleen and the kidney, is discussed with respect to the role played by these organs in the immune system of fish. Last, the lymphoid population in the gut associated lymphoid tissue (GALT) of turbot was characterised with respect to staining for Ig. Immunoreactive cells were rarely detected in the epithelial layer although many lymphocytes were present, but they were frequently observed in the lamina propria, presumably as part of the GALT and involved in mucosal immune responses.

Animals↗
PubMed1997

Expression of lymphocyte antigenic determinants in developing gut-associated lymphoid tissue of the sea bass Dicentrarchus labrax (L.).

The monoclonal antibodies DLT15 and DLIg3, which recognize antigenic determinants expressed by T cells and Ig-bearing cells, respectively, allowed the development of gut-associated lymphoid tissue of the teleost fish Dicentrarchus labrax (L.) to be studied. DLT15-immunoreactive cells were first detected in the epithelium of the stomach and intestine at day 30 post-hatching of fish maintained at 16 degrees C. At that age, positive cells were found only in the thymus. Between day 44 and day 81 post-hatching, DLT15-immunoreactive cells became numerous, both in and under the gut epithelium. A gradient in the number of lymphocytes was present, concentrating them towards the anus. Until day 81 post-hatching, DLIg3-immunoreactive cells were not found in the gut, although they were present in the kidney, spleen and thymus earlier. Infrequent Ig-bearing cells were found in the gut mucosa of -year-old sea bass. This study showed that the gut-associated lymphoid tissue developed earlier than other lymphoid compartments. It also provided evidence of the predominance of T cells in the gut immune system of the sea bass.

Aging↗
PubMed2004

Helicobacter pylori (H. pylori) molecular signature in conjunctival mucosa-associated lymphoid tissue (MALT) lymphoma.

Conjunctival mucosa-associated lymphoid tissue (MALT) lymphoma is an extranodal marginal zone B-cell lymphoma that is characterized by an exaggerated clonal expansion of B cells, which implicate a pathological proliferative response to antigen(s) including bacteria. Helicobacter pylori (H. pylori) infection is recognized as one of the causative agents of gastric MALT lymphoma; however, it has not been reported in extra gastric MALT lymphoma. We studied 5 patients (4 adults and 1 child) with salmon-colored conjunctival lesions. One patient also had a history of abnormal bone marrow biopsy a year earlier with lymphoid aggregates involving 5% of the overall bone marrow. The conjunctival lesions of the 5 patients were biopsied. Histopathological diagnoses were consistent with conjunctival MALT lymphoma. Lymphoma and normal conjunctival cells were microdissected using laser capture microscopy or manual techniques. DNA was extracted and subjected to PCR amplification using H. pylori gene-specific primers from the urease B and vac/m2 gene. Cells from chronic conjunctivitis (normal lymphocytes), conjunctival human T-cell lymphotropic virus type-1/adult T-cell leukemia/lymphoma (HTLV-1/ATL), and orbital B-cell lymphoma were also microdissected, processed and analyzed. PCR amplification and Southern blot hybridization demonstrated H. pylori DNA in the conjunctival MALT lymphoma cells of 4/5 cases. The negative case was the one with a history of abnormal bone marrow. In contrast, H. pylori gene was not detected in normal conjunctival cells from the cases of MALT lymphoma or the lymphocytes, ATL and orbital B-lymphoma cells from the controls. These data suggest that H. pylori may play a role in conjunctival MALT lymphoma.

Aged↗
PubMed2006

High-grade hepatic mucosa-associated lymphoid tissue (MALT) lymphoma probably transformed from the low-grade gastric MALT lymphoma.

The Mucosa-associated lymphoid tissue (MALT) lymphoma, which was first described in 1983, is known to be caused by chronic Helicobacter pylori (HP) infection, which triggers lymphoid infiltration and formation of organized lymphoid tissue. In approximately two thirds of cases of MALT, the lymphoma has been observed to regress after treatment of H. pylori infection; this provides strong evidence of a causative role of HP in the etiology of MALT. We report a case of a 67-year-old female patient with a high-grade MALT lymphoma of the liver; this occurred six years after complete remission of a low-grade gastric MALT lymphoma and after complete eradication of H. pylori. there was no recurrence of the previous low-grade gastric MALT lymphoma. Based on radiological and pathologic findings, the high-grade MALT was considered to result from transformation of the low-grade gastric MALT lymphoma.

Aged↗
PubMed1998

Expression of the lymphotoxin beta receptor on follicular stromal cells in human lymphoid tissues.

The lymphotoxin beta receptor (LTbetaR), and its ligand, LTalpha1beta2, have been proposed to play a key role in the development and organization of lymphoid tissues. The LTbetaR is expressed on a variety of human primary and transformed cells, but strikingly absent on T or B lymphocytes and primary monocytes or peripheral dendritic cells, although LTbetaR is detected on some myeloid leukemic lines. In the developing thymus LTbetaR is prominent along the trabeculae and into the medulla upto corticomedullary junction. In the spleen, LTbetaR is prominently expressed by cells in the red pulp and along the borders of red and white pulp which colocalizes with reticular stromal cells. The LTbetaR is expressed on a human follicular dendritic cell line, FDC-1, and signals expression of CD54 when ligated with the LTalpha1beta2 complex. These results support the concept that directional interactions between LTalpha1beta2 bearing lymphocytes and LTbetaR bearing stromal cells are involved in the organization of lymphoid tissue.

Cell Line↗
PubMed1997

A study of bronchus-associated lymphoid tissue in a rat model of chronic pulmonary infection with Pseudomonas aeruginosa.

The immunologic pathogenesis of conditions characterized by chronic pulmonary infections, such as diffuse panbronchiolitis and those associated with cystic fibrosis, had not been fully clarified. Organized lymphoid tissue along the airway has been termed bronchus-associated lymphoid tissue (BALT), and hyperplasia of BALT is frequently observed in chronic pulmonary infections in humans. To investigate the role of BALT, we intratracheally inoculated rats with Pseudomonas aeruginosa (PA) enmeshed in agar beads according to the method of Cash et al., thereby establishing a chronic pulmonary infection model. Histopathological examination of tissue from this rat model revealed the accumulation of lymphocytes and foamy cells around bronchioles. This finding corresponds to chronic bronchiolitis in humans. Hyperplasia of BALT was also observed. Immunohistochemical examination demonstrated that Ia+ cells, helper T cells, surface IgM-positive (sIgM+) cells and sIgA+ cells had gradually increased in BALT and the walls of peripheral airways during the period from day 4 to 7. The anti-PA IgA antibody titer in bronchoalveolar lavage fluid (BALF) was also elevated during this period. After day 21, non-helper T cells became predominant in tissue sections, and the numbers of various immunoglobulin-positive cells as well as the anti-PA IgA antibody titer in BALF were reduced. Histological examination revealed that the inflammatory findings had also diminished. The time course of changes in the various immune cells in BALT and the walls of peripheral airways, paralleled the reductions in anti-PA IgA antibody titers in BALF. Our findings suggest that hyperplastic BALT may be one source of the Ig producing cells which play an important role in the local immune response characteristic of chronic pulmonary infections.

Animals↗
PubMedDate not supplied

Cetirizine decreases interleukin-4, interleukin-5, and interferon-gamma gene expressions in nasal-associated lymphoid tissue of sensitized mice.

Although the action of cetirizine dihydrochloride (cetirizine), a potent histamine H1 receptor antagonist, has been well known, its effect on the cytokine profiles in the nasal immune inductive site has not been elucidated yet. We studied the effect of cetirizine on the cytokine profiles in the nasal-associated lymphoid tissue (NALT), which is a principal mucosal lymphoid tissue of the respiratory tract in rodents. Two different doses of cetirizine were given intraorally for 5 days before the nasal challenge of ovalbumin in sensitized mice. The sensitized group was given normal saline instead of cetirizine, and the nonsensitized group had no sensitization or medication. The cytokine gene expressions in the NALT taken from the mice were investigated with real-time quantitative reverse-transcription polymerase chain reaction. The effect of cetirizine on the allergic symptom score, histamine threshold, and the eosinophil count in the nasal septal mucosa were examined also. Compared with the normal mice, the sensitized mice showed significantly increased levels of interleukin (IL)-4 and IL-5 gene expression although the increase of interferon (INF)-gamma gene expression was not significant. In the cetirizine groups, the levels of expression of IL-4, IL-5, and INF-gamma in the NALT were significantly decreased compared with the sensitized group. The cetirizine groups also showed decreased allergic symptom score, histamine threshold, and eosinophil count in the nasal septal mucosa compared with the sensitized group. In conclusion, cetirizine reduced the levels of expression of IL-4, IL-5, and INF-gamma in the NALT of ovalbumin-sensitized mice. Cetirizine also reduced the acute allergic symptom, histamine sensitivity, and eosinophil count in the nasal septal mucosa.

Airway Resistance↗
PubMed1990

Fibronectin and the adhesive properties of rat lymphocytes obtained from different peripheral lymphoid tissues.

A comparative investigation has been carried out on the effect of plasma fibronectin (Fn) on the adhesive properties of normal rat lymphocytes obtained from different lymphoid tissues: blood, spleen, mesenteric and tonsillar lymph nodes. Fn was immobilized on the basis of its ability to bind to gelatin. We established that concentrations of 40-50 micrograms/ml are sufficient for a saturation effect on Fn coating. For spleen cells an adhesion of 55.7 +/- 9.3%, for mesenteric lymph nodes 34.5 +/- 8.7% and for tonsillar cells 33.8 +/- 3.2% was observed. Blood lymphocytes showed the lowest adhesion, 21.3 +/- 4.2%. Compared to the other lymphoid tissues, the spleen cells exhibited a "basal" adherence to surfaces coated with gelatin only: 19.2 +/- 4.1%. T lymphocytes participate to a greater extent in the process, since their number was significantly reduced in cell suspensions after adhesion to both gelatin and gelatin-Fn coated surfaces. The addition of soluble Fn leads to a competitive inhibition of the lymphocyte adhesion to gelatin-Fn coated surfaces. The data demonstrated the important role of Fn for the adhesive interactions of lymphocytes during their functional distribution in the tissues.

Animals↗
PubMed2002

Lymphomas of mucosal-associated lymphoid tissue in common variable immunodeficiency.

Common variable immunodeficiency (CVID) is a primary immunodeficiency disease characterized by low serum immunoglobulins IgG, IgA, and usually IgM. The central immune deficiency is impaired secretion of immunoglobulins and lack of antibody production; however, T cell dysfunction and a variety of inflammatory complications suggest global immune dysregulation. A number of reports have documented the association of primary immunodeficiency diseases with the development of non-Hodgkin's lymphoma (NHL). In CVID, the risk has been estimated to lie between 1.4% and 7%. As for NHL arising in other immunodeficiency states, the lymphomas in CVID are extranodal and are usually B cell in type. Of 22 B cell lymphomas that have appeared over a period of 25 years in a cohort of subjects with CVID, five lymphomas, appearing in more recently studied subjects, that arose in mucosal sites would be classified as mucosa-associated lymphoid tissue (MALT) lymphomas. MALT lymphomas are low-grade B cell lymphomas that result from a proliferation of neoplastic marginal-zone related cells of lymphoid tissue and tend to occur in organs that have acquired lymphoid tissue due to long-term infectious or autoimmune stimulation. Lymphomas of this kind have not been described in patients with congenital immunodeficiency, although chronic mucosal antigen stimulation is an integral part of these immune deficiency states.

Adolescent↗
PubMedDate not supplied

Fornix and conjunctiva reconstruction by amniotic membrane in a patient with conjunctival mucosa-associated lymphoid tissue lymphoma.

BACKGROUND: Conjunctival mucosa-associated lymphoid tissue (MALT) lymphoma is a rare, low-grade, non-Hodgkin's B-cell lymphoma. Herein, we report our successful management of the large conjunctival defect caused by resection of conjunctival MALT lymphoma by covering it with transplanted amniotic membrane. CASE: A 28-year-old Japanese man, who had been diagnosed histologically as having conjunctival MALT lymphoma in his left eye, was referred to us for treatment. The tumor was located on the lower bulbar and palpebral conjunctiva, and involved the fornix. Extensive resection of the conjunctival lesion was performed. Two pieces of amniotic membrane were used to reconstruct the fornix, bulbar, and palpebral conjunctival defect. OBSERVATIONS: Epithelialization over the transplantation was completed within 3 weeks when all sutures were removed. During the 6 months of follow-up, there was no recurrence or any postoperative complication, such as graft rejection, symblepharon, or chronic inflammation. CONCLUSIONS: We demonstrated for the first time that amniotic membrane can be used to cover a large defect on both bulbar and palpebral conjunctiva when such a low-grade malignancy as MALT lymphoma is extensively excised. Amniotic membrane transplantation was quite effective for the fornix and conjunctival reconstruction.

Adult↗
PubMedDate not supplied

Non-Hodgkin's lymphoma of mucosa-associated lymphoid tissue.

The concept of mucosa-associated lymphoid tissue (MALT) lymphomas was introduced by Isaacson and Wright [Cancer 1983; 52:1410-1416] in 1983. After more than 20 years of clinical research MALT lymphomas are now recognized as a distinct subtype of non-Hodgkin's lymphoma (NHL) with unique pathogenic, histological, and clinical features. Although this subtype of NHL occurs frequently, optimal management remains elusive. This manuscript reviews features of the clinical presentation, diagnosis, pathology, molecular characteristics, and management of both gastric and non-gastric MALT lymphoma.

Humans↗
PubMed1998

Apoptotic fraction in lymphoid tissue of FIV-infected SPF cats.

In the present study the apoptotic fraction has been investigated in peripheral blood mononuclear cells (PBMCs) and in lymphoid tissue of six clinically asymptomatic serologically positive specific pathogen free (SPF) FIV-infected cats with a decline in peripheral blood CD4+ lymphocytes, compared to five FIV- SPF controls. Apoptosis in PBMCs was scored in relation to cell cycle phases judged by the integrating cytometric measure of DNA content with 3H-thymidine and 3H-leucine incorporation. Apoptosis in lymphoid tissue was revealed with the ApopTag-peroxidase kit, quantified by image analysis and expressed as apoptotic index (number of apoptosis per 100 cells). The high percentage of apoptotic death in lymphocytes from FIV+ cats was chronologically related to the entrance of cells in the S phase of the cell cycle (p < 0.0001). No difference in the apoptotic index was revealed comparing the follicular, cortical + paracortical and medullary compartments in lymph nodes of FIV+ and FIV- cats. In each group of cats a similar pattern of apoptosis expression was revealed in lymph nodes: significantly higher in follicular vs. both cortical + paracortical and medullary compartments (p < 0.001). In the thymus a significant increase in apoptotic index was revealed in the cortical compartment of the FIV+ cats compared to FIV- (p < 0.001), while in the spleen both the red and white pulp expressed a higher value in FIV+ cats compared to FIV-(p < 0.05) and the former showed a pattern of expression as follows: in the red pulp significantly higher than in the white pulp (p < 0.001). This investigation suggests that the priming signals for apoptosis in FIV infection parallels the S phase of the cell cycle and peripheral blood changes could follow both thymic and splenic modifications in apoptotic expression.

Animals↗