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PubMed1996

[A case of bilateral MALT (mucosa-associated lymphoid tissue) type conjunctival malignant lymphoma].

A case of bilateral MALT (mucosa-associated lymphoid tissue) type conjunctival malignant lymphoma is reported. The patient, a 32 year old female, was referred to our hospital with the diagnosis of allergic conjunctivitis. We performed histopathological, immunohistochemical, and molecular genetical examination. The histopathological findings showed proliferation of CCL (centrocytelike) cells, lymphoepithelial lesion, and follicular colonization. Monoclonality of the tumor cells was revealed by molecular genetical analysis. On the basis of these detailed examinations, the patient was diagnosed as having MALT type malignant lymphoma. MALT type malignant lymphoma was first described by Isaacson in 1983. Both histological and clinical features are characteristic and quite different from other lymphomas. Some patients are affected bilaterally. Immunohistochemical and molecular genetical examinations in MALT type malignant lymphomas were found to be useful.

Adult↗

PubMed1997

Reassessment of gastric lymphoma in light of the concept of mucosa-associated lymphoid tissue lymphoma: analysis of 53 patients.

BACKGROUND: The concept of mucosa-associated lymphoid tissue (MALT) lymphoma is now widely accepted. However, precise characterization of the features of MALT lesions in the stomach is needed. For this, extensive analysis of resected gastrectomy specimens from a large number of patients with MALT lymphoma is essential. METHODS: Fifty-three patients who underwent gastrectomy for the treatment of primary gastric lymphoma were studied. In the histologic examination, a mean of 46 specimens per case were analyzed; the distribution of lymphomatous lesions was plotted on maps of gastrectomy specimens, input into a computer, and used to measure the size of lesions. RESULTS: The median age of the patients was 56 years, and the male-to-female ratio was 27:26. Stage of disease was I(E) for 35 patients, II(E) for 15, and III for 3. Histologically, 25 patients had low grade lesions, 18 had combined high and low grade lesions, and had 10 high grade lesions. Macroscopically, low grade MALT usually had multiple instances of superficial spreading of lesions without ulceration, whereas high grade MALT exhibited a solitary tumor-forming lesion. All of the superficial spreading type without ulceration were low grade MALT. The higher the grade of tumor, the larger the tumor size. Twenty-four patients received chemotherapy. The 5-year survival rate was 67.2%. Multivariate analysis revealed that only the clinical stage was a significant factor in prognosis. CONCLUSIONS: Low grade MALT can be differentiated from other types of MALT by macroscopic findings. When the MALT concept is adopted, stage of disease is important in relation to survival.

Adult↗

PubMed1995

Blood microvascular organization of the nasal-associated lymphoid tissue of the guinea pig: a scanning electron microscopic study of corrosion casts.

It has previously been confirmed that the guinea pig has aggregations of 10-20 lymphoid follicles at the junction of the nasal cavity and the nasopharyngeal duct. The vascular architecture of this nasal-associated lymphoid tissue (NALT) was studied by the corrosion cast/scanning electron microscope method. The NALT was supplied by branches of the inferior nasal artery. These afferent arterial branches gave off arterioles to the follicles and the interfollicular regions, where the arterioles ramified into capillaries. Some of these arterioles reached the subepithelial region to form a single-layer dense capillary network. The subepithelial capillaries gathered into short collecting venules, which in turn drained into high endothelial venules (HEV) in the interfollicular region. The HEV, which also receives tributaries from the follicular and interfollicular capillary plexuses, descended in the interfollicular regions and finally flowed into the efferent veins at the bottom of the NALT. Indentations impressed by high endothelial cells (HEC) were prominent on the surface of the HEV casts, and their frequency was larger in the upper course or segments than in the lower. This suggests that the incidence of HEC in the upper segments is higher than in the lower segments, and these findings are consistent with the hypothesis that some substances which are taken up into the subepithelial capillaries and transported to the venules induce differentiation and maintain of HEVs.

Animals↗

PubMed2007

MALT1, BCL10 and FOXP1 in salivary gland mucosa-associated lymphoid tissue lymphomas.

In view of the certain anatomic site-dependent frequency of chromosomal translocations involved in extranodal marginal zone B cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) pathogenesis, 17 salivary gland MALT lymphoma cases were analyzed for MALT1 and FOXP1 translocations. B cell CLL/lymphoma 10 (BCL10) and forkhead box PA (FOXP1) protein expression were studied by immunohistochemistry and translocations identified using fluorescence in situ hybridization (FISH)-specific probes FOXP1, t(11;18)(q21;q21)/API2-MALT1 and t(14;18)(q32;q21)/IgH-MALT1. None of the 11 analyzed cases showed FOXP1 rearrangement or amplification. The t(11;18) was present in five of 13 cases and the t(14;18) in three of 13 cases. MALT1 translocations were mostly mutually exclusive except in a single case. FOXP1 protein expression showed differences in the proportion of tumor cells with nuclear expression but not in their intensity, with the exception of one case where very intense nuclear staining was noted. BCL10 nuclear expression was present in four of 17 cases, two of which lacked t(11;18). Our results suggest that MALT1-specific translocations and FOXP1 rearrangements are not commonly involved in pathogenesis. A case with strong FOXP1 protein expression indicates the possibility that the upregulation of FOXP1 expression is significant in a small subset of salivary gland MALT lymphomas. Also a single case in which both MALT1 translocations were present indicates that these are not always mutually exclusive.

Adaptor Proteins, Signal Transducing↗

PubMed1999

The significance of bronchus-associated lymphoid tissue in human lung transplantation: is there an association with acute and chronic rejection?

BACKGROUND: In animal models of acute rejection in lung allografts, bronchus-associated lymphoid tissue (BALT) plays a major role in the induction and persistence of the alloreactive response. We undertook a study of the clinical and histologic associations with BALT identified on transbronchial biopsy in human lung allograft recipients. METHODS: Transbronchial biopsies of patients receiving single lung, double lung, and combined heart-lung transplantation from 1984 to 1997 at the University of Pittsburgh Medical Center were reviewed. Seventy-seven patients had transbronchial biopsies demonstrating BALT. We examined all pathologic reports and slides, and graded rejection utilizing the Revised Working Formulation for the Classification of Pulmonary Allograft Rejection. Twenty-nine of 77 patients were selected at random to evaluate the distribution of BALT lymphocyte subsets immunohistochemically. RESULTS: There was no relationship between native disease or the transplant procedure and the identification of BALT. BALT was found from 9 days to 2431 days after transplant (average: 440 days; median: 157 days) in association with clinically insignificant acute cellular rejection (A0, A1) in 75% of cases. Bronchiolitis obliterans developed in 29% of patients with a BALT-positive biopsy, a percentage not different from that of our overall lung transplant population. Immunohistochemical examination of BALT showed helper T cells predominated over cytotoxic T cells in zones surrounding B cell-rich follicular center cells. CONCLUSIONS: The association of BALT with high-grade acute cellular rejection and with the development of bronchiolitis obliterans could not be confirmed in human lung allografts. BALT most often accompanied A0 or A1 rejection. This raises the possibility that the presence of BALT on transbronchial biopsy may be part of the evolution of immunologic tolerance in human pulmonary allografts.

Acute Disease↗

PubMed2000

Human immunodeficiency virus type 1 coreceptor preferences determine target T-cell depletion and cellular tropism in human lymphoid tissue.

The present study sought to determine how usage of coreceptors by human immunodeficiency virus type 1 dictates cell tropism and depletion of CD4(+) T cells in human lymphoid tissues cultured ex vivo. We found that coreceptor preferences control the marked, preferential depletion of coreceptor-expressing CD4(+) lymphocytes. In addition, there was a strong, but not absolute, preference shown by CXCR4-using strains for lymphocytes and by CCR5-using strains for macrophages.

CD4-Positive T-Lymphocytes↗

PubMed1985

A monoclonal antibody that detects HLA-D region antigen in routinely fixed, wax embedded sections of normal and neoplastic lymphoid tissues.

We describe the use of a monoclonal antibody (TAL-IB5) to HLA-D region alpha-chains that reacts well with HLA-D positive cells in normal and neoplastic lymphoid tissues fixed in routine fixatives and embedded in paraffin wax in the conventional fashion. This antibody should prove to be useful in routine histological investigations of lymphoid and possibly other neoplasms as well as other non-neoplastic conditions where the immune system plays an important part.

Antibodies, Monoclonal↗

PubMed1992

Histopathologic and immunohistochemical changes in gut-associated lymphoid tissues after treatment of rabbits with dexamethasone.

Corticosteroids cause impaired cell-mediated immunity which may encourage development of gastrointestinal and respiratory infections. In order to better understand the effects of corticosteroids on gastrointestinal immunity, immunological and histological changes in gut-associated lymphoid tissues were examined after intravenous administration of dexamethasone to rabbits. In treated animals, lymphoid domes and follicles were considerably reduced in size, and the dome epithelial layer was markedly depleted of M cells and lymphocytes. There were numerous open lesions at the luminal surface of dome epithelium, consistent with necrosis of M cells, and a striking depletion of follicular B cells in treated animals. These immunologic and histologic effects of corticosteroids could have found profound, deleterious effects on mucosal immune responses and host resistance to microbial infections.

Animals↗

PubMed1995

Defective bronchus-associated lymphoid tissue in long-term surviving rat lung allografts.

In a previous study we found that a local immune response did not develop in the bronchus-associated lymphoid tissue (BALT) of infected rat allografts. We hypothesized that the BALT in rat lung allografts was damaged after allotransplantation. Therefore, we investigated three prerequisites for a normal function of the BALT, i.e., its structure, the uptake of antigens, and the lymphocyte migration to the BALT in three groups of rats (n = 10 each): (1) Brown Norway(BN)-to-Lewis (LEW) allografts; (2) LEW-to-LEW isografts; and (3) normal LEW rats. All rats were immunosuppressed with CsA (injected on days 2 and 3). Six mo after transplantation the structure of the BALT and the uptake of intrabronchially injected carbon particles in the BALT were determined histologically; the migration of intravenously injected, fluoroscein-isothiocyanate labeled lymphocytes to the BALT was determined immunohistochemically. In the allografts the BALT was defective in all three investigated aspects. It was reduced in size and lymphocyte density and was largely replaced by fibrous tissue. Twenty-four h after administration no carbon particles and only a few labeled lymphocytes were found in the BALT. In contrast, in the syngeneically transplanted and nontransplanted lungs the BALT consisted of a large and dense collection of lymphocytes. In these BALTs large numbers of carbon particles and labeled lymphocytes were found. In conclusion, after allogeneic transplantation the BALT in the lung becomes defective in structure and function. The BALT is most likely damaged by rejection, since the BALT is syngeneic lung transplants was perfectly normal.

Animals↗

PubMed1993

Kinetics of B cell subpopulations in peripheral lymphoid tissues: evidence for the presence of phenotypically distinct short-lived and long-lived B cell subsets.

A small proportion of the sIg+ B lymphocytes in peripheral lymphoid organs [22% in spleen and 6% in lymph node (LN)] in rat carries the Thy-1 antigen. These Thy-1+ B cells represent newly formed bone marrow (BM) derived (or immature) B cells. In this study we investigated the kinetic behavior of Thy-1+ and Thy-1- B cells in various lymphoid tissues. The renewal rates of these B cells in young adult rats were determined by continuous administration of 5-bromo-2-deoxyuridine (BrdU) for up to 6 weeks. At several time intervals, Thy-1+ and Thy-1- B cell subpopulations in BM, blood, spleen and popliteal LN were analyzed for the presence of incorporated BrdU, using three-color immunocytology on cytospin preparations. In all tissues studied, the Thy-1+ B cells were rapidly renewed with a rate that varied between 58% (BM) and 22% (LN) per day. Virtually all Thy-1+ B cells were labeled by BrdU within a period of 8-16 days, indicating that all these cells are relatively short-lived. By contrast, the replacement of Thy-1- B cells in these tissues was 30-40 times lower, and ranged between 2.0 and 0.8% per day. In absolute numbers we estimate that 57 million Thy-1+ B cells are renewed per day in the BM whereas only 10 million Thy-1- B cells are replaced in the pool of long-lived peripheral B cells. This implicates a cell loss of 80% at the transition of the Thy-1+ to the Thy-1- B cell stage. The few B cells that actually become incorporated into the pool of mature B cells are most probably selected on the basis of the specificity of their sIg.

Animals↗

PubMed1988

Histopathological studies of experimental marine toxin poisoning. II. The acute effects of maitotoxin on the stomach, heart and lymphoid tissues in mice and rats.

Maitotoxin, one of the causative agents of ciguatera isolated from marine dinoflagellate, Gambierdiscus toxicus, induced severe pathomorphological changes in the stomach, heart and lymphoid tissues in mice and rats. Multiple erosions were observed in gastric mucosa accompanied by a marked increase in total calcium content 24 hr after i.p. injection of 200 or 400 ng/kg of maitotoxin. In contrast, there was no close temporal association between the accumulation of calcium and the morphological appearance of dead cells in the heart and thymus. Within 30 min of administration of 200 or 400 ng/kg of maitotoxin, a marked swelling was seen in the endothelial lining cells of blood capillaries between cardiac muscle fibers, followed by the cell death of the fibers. Injection of maitotoxin at a dose of 200 ng/kg or higher also resulted in necrosis of lymphocytes in the cortex of the thymus at 4 hr and in the medulla at 8 hr.

Animals↗

PubMed1991

The neuroimmune link in the bronchus-associated lymphoid tissue (BALT) of cat and rat: peptides and neural markers.

This light microscopic immunohistochemical study investigates the distribution and target interrelations of nerve fibers in bronchus-associated lymphoid tissues (BALT) of rat and cat by using antisera against (1) the polyneuronal marker protein gene product 9.5 (PGP 9.5), (2) selected opioid and nonopioid peptides, and (3) the marker enzymes tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH). In both species, a similar distribution pattern of PGP, peptide, and catecholamine enzyme immunoreactive was observed. Anti-PGP 9.5 stained all nerve fibers (except some smaller, calcitonin gene-related peptide-immunoreactive (CGRP-ir) fibers presumably of the C-type) throughout the different compartments of BALT, e.g., under the epithelium, in the smooth muscle layer, along the vasculature, and between immune cells of BALT parenchyma. The distribution of fibers staining for peptides (substance P (SP), (CGRP), neuropeptide Y (NPY). Leu-enkephalin, Met-enkephalin-Arg-Gly-Leu) and/or the catecholamine enzymes was also not compartment-specific. However, the density of the different peptidergic fibers and those staining for the marker enzymes exhibited region- and target-specific variations, e.g., fibers, cocontaining substance P and CGRP were more ubiquitous in nonvascular regions than codistributed NPY-, TH-, and DBH-ir fibers, which clearly prevailed in perivascular plexus. Regularly, nerve fibers staining for any of the peptides and markers investigated formed close contacts with mast cells, cells of the macrophage/monocyte cell line (identified as ED1 + cells), and/or other lymphoid cells, although with different frequencies. We assume that the SP/CGRP innervation is mainly of primary sensory origin, while the NPY innervation is chiefly derived from postganglionic noradrenergic sympathetic neurons. The VIP/PHI component is most likely postganglionic cholinergic while the opioid component, apparently derived from the Proenkephalin precursor, could be of differential origin. We propose that the neuroimmune connections in BALT play a significant role in the regulation and/or modulation of physiological/pathophysiological mechanisms of the lung. BALT may also be an integral part of the psycho-neuro-immune axis.

Amino Acid Sequence↗

PubMed1978

[Development of hematopietic and lymphoid tissues in conjoint bone marrow and thymus transplants].

The model of heterotopic transplantation of the mixture of bone marrow and thymus fragments was used to study the interaction of hemopoietic and lymphoid tissues under their direct contact. The bone marrow and thymus fragments of adult mice F1 (CBAXXC57BL) were transplanted separately or in the mixture under the kidney capsule of mice of the same strain. During the whole period of observation (from 10 days up to 14 months), the development of bone marrow and thymus fragments in the joint transplants proceeded independently, no "mixed" stroma appeared, and the stroma of each organ ensured the differentiation characteristic of its organ. The development of joint transplants somewhat differs from that of isolated transplants: on the 10th day a greater amount of hemopoietic tissues was noted in the former; the bone marrow component increases continuously up to 6 months (vs. 1--2 months in the isolated transplants); the bone and hemopoietic tissues predominate in the joint transplants by 14 months, the amount of thymic tissue markedly decreases but it does not disappear completely.

Animals↗

PubMedDate not supplied

Developmental study of immunocompetent cells in the bronchus-associated lymphoid tissue (BALT) from Wistar rats.

The aim of the present report was to study in growing Wistar rats the development of immunocompetent cells in the bronchus-associated lymphoid tissue (BALT). We found at day 4 postpartum, a high number of TCRgamma/delta+ T cells and very few CD8alpha+, CD8beta+, CD5+, TCRalpha/beta+ T cells in BALT. The latter cells and CD4+ T cells increase with age. Even though T cells expressing TCRgamma/delta outnumber those expressing TCRalpha/beta early in development, until 45 days of age, alpha/beta+ predominate over gamma/delta+ T cells only in adult rats (60 days of age). Moreover, a predominance of suppressor/cytotoxic T cells over T-helper cells was found in 60 days old rats. Surprisingly, more CD8alpha+ than CD8beta+ T cells in BALT are observed. The number of IgA+ B and CD4+ T cells found in the BALT increases with age. The early appearance - 4 days of age - of all T-cell phenotypes in BALT especially of gamma/delta+ T cells may imply a benefit to respond to inhaled antigen soon after birth.

Aging↗

PubMed1996

Induction of CYP1A1 and ALDH-3 in lymphoid tissues from Fisher 344 rats exposed to 2,3,7,8-tetrachlorodibenzodioxin (TCDD).

The immune system is a primary target for toxic insult by a number of drugs and environmental chemicals, many of which require activation to toxic metabolites by drug-metabolizing enzymes. We compared the induction of drug-metabolizing enzymes, including cytochrome P450 1A1 (CYP1A1) and aldehyde dehydrogenase (ALDH), in lymphoid tissues of F344 rats following treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). ALDH was induced in both the spleen and the thymus after TCDD treatment, with maximal expression at 9 and 15 days, respectively. Thymic microsomal preparations from TCDD-treated animals expressed elevated levels of inducible CYP1A1 as compared to microsomes from the spleens of treated animals or tissues from control rats. TCDD treatment also resulted in increased ethoxyresorufin-O-deethylase (EROD) activity in the thymus. There were no detectable mRNA transcripts for CYP1A1 in peripheral blood or splenic lymphocytes from treated animals; however, CYP1A1 transcripts were induced in isolated thymocytes, whole spleen, and whole thymus. In vitro exposure to TCDD did not result in induction of immunoreactive CYP1A1 in thymocytes unless simultaneously activated with the mitogen, phytohemagglutinin (PHA). Immunohistochemical localization of CYP1A1 in immune tissues indicated that cells other than the lymphoid populations are responsible for the increased CYP1A1 expression. The pattern of CYP1A1 induction was related to the expression of the Ah receptor (AhR) in immune tissues. Western blot analyses demonstrated less AhR present in peripheral blood lymphoid cells and spleen, as compared to whole tissues. These studies indicate that while drug-metabolizing enzymes are present in immune tissues, the induction of enzymes is selective in different lymphoid cells.

Aldehyde Dehydrogenase↗

PubMed2004

Development of T lymphocytes in the nasal-associated lymphoid tissue (NALT) from growing Wistar rats.

The aim of the present report was to study the development of several T-lymphocyte subsets in the nasal-associated lymphoid tissue (NALT) of growing Wistar rats. CD5+ and CD4+ lymphocytes gradually increased with age. A predominance of CD8alpha+ over CD4+ T cells was found from 7 to 45 days but from 45 to 60 days of age T helper cells outnumbered the cytotoxic subpopulation. The majority of CD8+ T lymphocytes expressed the heterodimeric isoform. The most relevant findings by immunohistochemistry are: (1) the predominance of TCRgammadelta+ and CD8alpha+ cells at 7 days postpartum over all the other T-cell subpopulations; and (2) that TCRgammadelta+ outnumbered TCRalphabeta+ T cells from 7 to 45 days postpartum whereas alphabeta T cells predominated in 45- and 60-day-old rats. Besides, cytometric studies have shown that the percentages of TCRgammadelta+, CD8alpha+, as well as the population coexpressing both phenotypes (TCRgammadelta+CD8alpha+), were significantly higher in rats at 7 days postpartum when compared to 60 day-old rats. In the present study, the finding of a high number of gammadelta+ and CD8+ T cells early in NALT development may indicate the importance of these subpopulations in the protection of the nasal mucosa in suckling and weaning Wistar rats.

Age Factors↗

PubMed1986

Immunoreactivity for S-100 protein in dendritic and in lymphocyte-like cells in human lymphoid tissues.

S-100 protein is an immunohistochemical marker for a subset of dendritic cells, the interdigitating reticulum cells (IDRCs), which are mainly located in T-dependent areas of lymphoid tissues. In the present study we have investigated the distribution of S-100-positive cells in lymph nodes, spleen, thymus and peripheral blood of normal subjects. Immunoreactivity for S-100 protein was demonstrated in large cells with dendritic morphology and in small lymphocyte-like cells present in the lymph node paracortex, thymic medulla, splenic periarterial lymphatic sheaths (PALS) and in peripheral blood. S-100-positive lymphocyte-like cells were frequently detected around high endothelial venules (HEV) and were present in numbers comparable to those of S-100-positive IDRCs. Immunoelectron microscopy confirmed the existence of positive cells with lymphoid morphology and revealed that the intracellular distribution of the immunoreaction product was similar in lymphoid and dendritic cells. Further characterization of S-100-positive cells demonstrated that both lymphoid and dendritic cells were unreactive with a large panel of monocytic and macrophage markers.

Antigens, Differentiation, T-Lymphocyte↗

PubMed1989

[Immunity of gut-associated lymphoid tissue and the role of the oral immunotherapy in multi-disciplinary treatment of the digestive organ cancer].

In order to augment antitumor immunity of gut-associated lymphoid tissue in digestive organ cancer, oral administration of various biological response modifiers were studied using mice transplanted with cecal tumor. Among them OK-432 was the most effective and clinical application of oral OK-432 was studied. Autoradiogram and immunofluorescence studies showed the absorption of orally administered OK-432 from the gut. In phase I study oral OK-432 was much less toxic than other administration routes. Phase II study showed that oral OK-432 at various doses augmented antitumor immunity of the lymphocytes of peripheral blood and regional lymph node. In a multi-institutional study on postoperative adjuvant immunotherapy, 1011 gastric cancer patients were accumulated and randomized to compare the effects of oral and intradermal OK-432. In patients who underwent curative operation, 1-, 2- and 3-year survival rates (%) were 95, 88 and 82 for oral OK-432 group (n = 255), 88, 83 and 80 for the placebo group (n = 260), and 89, 79 and 73 for intradermal OK-432 group (n = 261). There was significant differences among cumulative survivals of three groups, and this life-prolonging effect of oral OK-432 was remarkable for stage II or III patients. These results demonstrate that oral immunotherapy with OK-432 is useful as an immunotherapy of digestive organ cancers.

Administration, Oral↗