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PubMed1999

The apoptosis inhibitor gene API2 and a novel 18q gene, MLT, are recurrently rearranged in the t(11;18)(q21;q21) associated with mucosa-associated lymphoid tissue lymphomas.

Marginal zone cell lymphomas of the mucosa-associated lymphoid tissue (MALT) are the most common subtype of lymphoma arising at extranodal sites. The t(11;18)(q21;q21) appears to be the key genetic lesion and is found in approximately 50% of cytogenetically abnormal low-grade MALT lymphomas. We show that the API2 gene, encoding an inhibitor of apoptosis also known as c-IAP2, HIAP1, and MIHC, and a novel gene on 18q21 characterized by several Ig-like C2-type domains, named MLT, are recurrently rearranged in the t(11;18). In both MALT lymphomas analyzed, the breakpoint in API2 occurred in the intron separating the exons coding respectively for the baculovirus IAP repeat domains and the caspase recruitment domain. The breakpoints within MLT differed but the open reading frame was conserved in both cases. In one case, the translocation was accompanied by a cryptic deletion involving the 3' part of API2. As a result, the reciprocal transcript was not present, strongly suggesting that the API2-MLT fusion is involved in the oncogenesis of MALT lymphoma.

Amino Acid Sequence↗

PubMedDate not supplied

L-arginine-enriched parenteral nutrition affects lymphocyte phenotypes of gut-associated lymphoid tissue.

BACKGROUND: Experimentally, total parenteral nutrition (TPN) diminishes gut-associated lymphoid tissue (GALT) cell numbers and function. Although glutamine supplementation is known to reverse TPN-induced changes in GALT, effects of another conditionally essential amino acid, L-arginine (ARG), on GALT remain unclear. METHODS: Twenty-two male Institute of Cancer Research mice were randomized to standard TPN (0.3% arginine, STD-total parenteral nutrition) or 1% ARG-enriched TPN (ARG-total parenteral nutrition). After 5 days of feeding, lymphocytes were harvested from Peyer's patches (PP), the lamina propria, and intraepithelial (IE) spaces of the small intestine to determine cell yields. Lymphocyte phenotypes (alphabetaTCR, gammadeltaTCR, CD4, CD8, and B220 as a B cell marker) were determined using flow cytometry. IgA levels in washings of the small intestine, upper respiratory tract, and lungs were measured with ELISA. RESULTS: ARG-total parenteral nutrition did not affect lymphocyte yields. The percentages of CD4+ cells in PP and IE, and alphabetaTCR+ cells in PP, were significantly higher in the ARG-total parenteral nutrition than in the STD-total parenteral nutrition mice, without marked differences in other phenotypes examined. There were no significant differences in intestinal and respiratory tract IgA levels between the 2 groups of mice. CONCLUSIONS: One percent ARG supplementation of TPN does not improve GALT cell number or mucosal IgA level but benefits to increase CD4+ cell percentages in GALT.

Animals↗

PubMed1997

Long-term follow-up of disappearance of gastric mucosa-associated lymphoid tissue after anti-Helicobacter pylori therapy.

OBJECTIVES: Mucosa-associated lymphoid tissue (MALT) can develop in gastric mucosa after Helicobacter pylori infection, but not all H. pylori-positive patients develop acquired MALT, probably because of different levels of individual susceptibility against H. pylori-antigens. Our aim was to conduct long-term follow-up in MALT-positive and MALT-negative patients after H. pylori had been eradicated to determine what happens after H. pylori reinfection. METHODS: We studied 30 H. pylori-positive patients, 15 MALT-positive patients (group A), and 15 MALT-negative patients (group B). After the eradication of H. pylori and disappearance of acquired MALT in group A, follow-up was conducted by repeated endoscopic biopsies every 4-6 months for a mean period of 30.6 months (31.6 months for group A, 29.4 for group B). RESULTS: During follow-up, three group A patients were reinfected by H. pylori, and MALT recurred. Moreover, in each patient, it was the same grade of acquired MALT that had previously been diagnosed (grade 2 in two patients and grade 3 in one). A second course of anti-H. pylori treatment resulted both in eradication of H. pylori and the disappearance of MALT. Conversely, none of the group B patients with H. pylori reinfection developed MALT. However, in those patients, too, a second course of treatment eradicated the H. pylori. CONCLUSIONS: Our study shows that acquired MALT appears after reinfection with H. pylori only in patients who previously had that condition. Moreover, the grade of acquired MALT that reappears is the same as previously diagnosed. These findings demonstrate that not only H. pylori infection but also individual susceptibility may be important in determining both the presence of acquired MALT and its grade. However, strict follow-up is not advisable in MALT-positive patients, because no patient developed MALT-lymphoma during follow-up.

Adult↗

PubMed2006

Peripheral blood B-cell death compensates for excessive proliferation in lymphoid tissues and maintains homeostasis in bovine leukemia virus-infected sheep.

The size of a lymphocyte population is primarily determined by a dynamic equilibrium between cell proliferation and death. Hence, lymphocyte recirculation between the peripheral blood and lymphoid tissues is a key determinant in the maintenance of cell homeostasis. Insights into these mechanisms can be gathered from large-animal models, where lymphatic cannulation from individual lymph nodes is possible. In this study, we assessed in vivo lymphocyte trafficking in bovine leukemia virus (BLV)-infected sheep. With a carboxyfluorescein diacetate succinimidyl ester labeling technique, we demonstrate that the dynamics of lymphocyte recirculation is unaltered but that accelerated proliferation in the lymphoid tissues is compensated for by increased death in the peripheral blood cell population. Lymphocyte homeostasis is thus maintained by biphasic kinetics in two distinct tissues, emphasizing a very dynamic process during BLV infection.

Animals↗

PubMed1987

Lymphoid tissue responses to perfluorocarbon emulsion in mice.

The effects of either intraperitoneal or intravenous injection of low doses (5 or 10 ml/kg) of the proprietary emulsified perfluorocarbon-based blood substitute, Fluosol-DA 20%, on mouse lymphoid tissue and antibody production against sheep erythrocytes (SRBC) have been investigated. Mean liver weight was significantly increased and gut mesenteric lymph node (MLN) weights decreased in all animals injected with Fluosol-DA, irrespective of route of administration. In contrast, spleen weight decreased following intravenous injection of emulsion at 5 ml/kg. The mean plasma haemagglutination response to SRBC was significantly (P less than 0.01) increased in animals injected intraperitoneally with Fluosol at both doses but was similar to control in all other cases. These results show that lymphoid tissue responses to Fluosol-DA in mice are variable and that antibody production against intraperitoneally-injected SRBC is enhanced by prior injection of emulsion into the peritoneal cavity.

Animals↗

PubMed1990

Low grade B cell lymphoma of gut-associated lymphoid tissue (GALT): a model of the structure and migration pathways of the B cell component of normal human GALT.

The histology, microenvironment and migratory pathways of low grade B cell lymphomas (LGBL) are thought to reflect those of normal lymphoid tissue of similar lineage. Striking clinical differences between LGBL of peripheral lymph nodes and those of the gastrointestinal tract serve to emphasize the lineage differences between mucosal and non-mucosal B cells and suggest that LGBL of gut-associated lymphoid tissue (GALT) could serve as a natural experimental model for the investigation of the properties of normal human GALT. The histology of LGBL of GALT parallels that of normal GALT and draws particular attention to the previously undescribed GALT marginal zone B cells which show close lineage homology with LGBL of GALT. These cells known as centrocyte-like (CCL) cells surround follicles, infiltrate the epithelium and frequently show plasma cell differentiation possibly in response to stimulation from the gut lumen. In LGBL of GALT the CCL cells have an intimate relationship with reactive follicles similar to that described for rat splenic marginal zone cells. LGBL of GALT are slow to disseminate to the periphery and can often be cured by local eradication. This suggests CCL cells do not enter the peripheral blood. However, the gastrointestinal tract remote from the primary tumour is occasionally selectively involved, a finding which supports circulation and homing as described in animals. Using a murine monoclonal anti-idiotypic antibody in one case of LGBL of GALT we have shown that CCL cells appear to enter the circulation and, in the absence of evident tumour, can be identified in the mucosae as well as the marginal zone of the spleen where they undergo plasma cell differentiation.(ABSTRACT TRUNCATED AT 250 WORDS)

B-Lymphocytes↗

PubMed2000

Regulation of TCL1 expression in B- and T-cell lymphomas and reactive lymphoid tissues.

Chromosomal rearrangements observed in T-cell prolymphocytic leukemia involve the translocation of one T-cell receptor gene to either chromosome 14q32 or Xq28, deregulating the expression of cellular protooncogenes of unknown function, such as TCL1 or its homologue, MTCP1. In the human hematopoietic system, TCL1 expression is predominantly observed in developing B lymphocytes, whereas its overexpression in T cells causes mature T-cell proliferation in transgenic mice. In this study, using a newly generated monoclonal antibody against recombinant TCL1 protein, we extended our analysis mainly by immunohistochemistry and also by fluorescence-activated cell sorting and Western blot to a large tumor lymphoma data bank including 194 cases of lymphoproliferative disorders of B- and T-cell origin as well as reactive lymphoid tissues. The results obtained show that in reactive lymphoid tissues, TCL1 is strongly expressed by a subset of mantle zone B lymphocytes and is expressed to a lesser extent by follicle center cells and by scattered interfollicular small lymphocytes. In B-cell neoplasia, TCL1 was expressed in the majority of the cases, including lymphoblastic lymphoma, chronic lymphocytic leukemia, mantle cell lymphoma, follicular lymphoma, Burkitt lymphoma, diffuse large B-cell lymphoma (60%), and primary cutaneous B cell lymphoma (55%). TCL1 expression was observed in both the cytoplasmic and nuclear compartments, as confirmed by Western blot analysis. Conversely, TCL1 was not expressed in Hodgkin/Reed-Sternberg cells, multiple myelomas, marginal zone B-cell lymphomas, CD30+ anaplastic large cell lymphoma, lymphoblastic T-cell lymphoma, peripheral T-cell lymphoma, and mycosis fungoides. These data indicate that TCL1 is expressed in more differentiated B cells, under both reactive and neoplastic conditions, from antigen committed B cells and in germinal center B cells and is down-regulated in the latest stage of B-cell differentiation.

Aged↗

PubMed1985

Application of image analysis for quantitative immunoperoxidase detection of IgE containing cells in lymphoid tissues.

Methods for the quantitation of antigen or antibody specific cells within lymphoid structures rely on the laborious and often inaccurate counting of stained cells visually under the microscope. To circumvent these problems we used a combination of computer-linked image analysis, with the Quantimet 720 and specific staining for IgE by immunoperoxidase, to produce a relatively easy, accurate method for the quantitation of specifically stained cells within tonsils and lymph nodes. Frozen sections of bovine lymph nodes and tonsils were stained in an indirect immunoperoxidase technique with either rabbit anti-bovine IgE or normal rabbit serum as the primary reagent. Examination of the stained slides on the Quantimet 720 image analyzing computer revealed cells that were sufficiently dark to be considered above the 'threshold level' of background staining. These were counted as positive picture points. A quantitative evaluation of the relative number of IgE containing cells within the particular lymphoid tissue was arrived at by determining the difference between the percent positive picture in the control tissue incubated with normal rabbit serum (background) and in the sample treated with rabbit anti-IgE. Using this method, it was readily possible to quantitate the presence of IgE containing cells in the tonsils of calves; the highest percentage of positive tissue was present in the tonsils of calves exposed to ovalbumin. Image analysis is a useful technique for quantitative evaluation of any immunoperoxidase stained tissues.

Animals↗

PubMed2000

Effects of early antiretroviral treatment on HIV-1 RNA in blood and lymphoid tissue: a randomized trial of double versus triple therapy. Swiss HIV Cohort Study.

To assess the effects of early initiation of antiretroviral therapy on cell-free and cell-associated viral load in blood and lymphoid tissue, we performed a randomized, open-label, multicenter trial comparing a double (zidovudine + lamivudine) and triple (zidovudine + lamivudine + ritonavir) drug combination in treatment-naive, asymptomatic patients with CD4 counts >400 cells/microl. HIV-1 RNA was measured in plasma, peripheral blood mononuclear cells, and sequential tonsil or lymph node biopsies (27 patients); the study follow-up was 2 years. Among 42 randomized patients, the proportion with plasma HIV-1 RNA <50 copies/ml was 16% and 74% at week 24 (p<.001) in those randomized to double and triple therapy, respectively, necessitating frequent treatment intensification in the double arm. After a rapid decline within 4 weeks in both arms, cell-associated HIV-1 RNA decreased further only in those patients with sustained suppression of plasma viral load, but remained almost always detectable at low levels, indicating persisting transcription of viral RNA. CD4 counts increased by 200 to 250 cells/microl at week 96 in both arms without significant differences (intent-to-treat analyses). Thus, even if treatment is initiated early in asymptomatic patients with preserved CD4 counts, three drugs are necessary to achieve sustained decreases of HIV load in blood and lymphoid tissue.

Adult↗

PubMed1990

Detection of immunoglobulin light-chain mRNA in lymphoid tissues using a practical in situ hybridization method.

The identification of immunoglobulin protein in routinely fixed and paraffin-embedded sections using antibodies combined with immunoperoxidase or similar techniques of detection is often problematic. We developed an in situ hybridization methodology for the identification of light-chain mRNA that is applicable to formalin-fixed, paraffin-embedded tissues, using either radiolabeled or biotinylated oligonucleotide probes based on the kappa and lambda light-chain gene-constant regions. Reactive plasma cells can be consistently identified in reactive lymphoid tissues, and a monotypic pattern of light-chain mRNA restriction was seen in each of eight cases of multiple myeloma/plasmacytoma. Immunoblasts and germinal center cells also are labeled in reactive lymphoid tissues. Using 355-labeled probes, 29 of 93 cases (30%) of non-Hodgkin's lymphomas had detectable light-chain mRNA, while 19% of non-Hodgkin's lymphomas were positive using biotinylated probes.

Autoradiography↗

PubMed1987

A histological and immunocytochemical study of lymphoid tissue in rectal biopsies from homosexual men.

A histological study of the lymphoid tissue of the rectums of 323 homosexual and 30 heterosexual men (including five intravenous drug users seropositive for human immunodeficiency virus, HIV) was undertaken. Marked lymphoid hyperplasia (germinal centre greater than 680 microns in diameter) was found in 13 men, nine of whom had a sexually transmitted infection of the rectum. Immunocytochemical studies showed that the germinal centres contained B-cells and follicular dendritic cells, surrounded by CD4+ and CD8+ T-cells in a ratio of between 5:1 and 10:1. In HIV-infected men there were decreased numbers of CD4+ cells and increased numbers of CD8+ cells, resulting in a ratio of between 0.8:1 and 2:1. In biopsies from four of seven HIV-infected men the follicular dendritic cell processes appeared shorter and fragmented. The pathogenesis of HIV infection is discussed in the light of these findings.

Biopsy↗

PubMed2000

Molecular detection of circulating neoplastic cells in patients with clinically localised gastric and non-gastric mucosa-associated lymphoid tissue lymphoma.

BACKGROUND: Unlike other low-grade lymphomas, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type usually presents with localised disease. AIM: To detect peripheral blood lymphoma involvement to establish the incidence of occult lymphoma dissemination. PATIENTS AND METHODS: In a series of 18 cases, peripheral blood was analysed by polymerase chain reaction, with primers directed to the third-complementarity determining region of the immunoglobulin heavy chain gene. RESULTS AND CONCLUSION: The presence of circulating neoplastic cells was detected in 21% of clinically localised cases. Moreover lymphoma cells were detected in 2 out of 6 morphologically normal bone marrow specimens. The present data show that, combining morphological and molecular methods, occult dissemination can be found in a large proportion of cases thus stressing the need for careful staging procedures. However, it has still to be clarified whether the presence of polymerase chain reaction-detectable circulating lymphoma cells can influence the outcome of mucosa-associated lymphoid tissue lymphoma patients submitted to antibiotic treatment (for gastric localisation) or local therapy (surgery or radiation, for non-gastric tumours).

Adult↗

PubMed2001

Changes in lymphocyte subsets in the bronchus-associated lymphoid tissue of goats naturally infected with different Mycoplasma species.

The distribution of cells containing lysozyme, S-100 protein, CD3, CD4, CD8, major histocompatibility complex class II antigen and immunoglobulin G (IgG) was analysed in the bronchus-associated lymphoid tissue (BALT) of goats naturally infected with three Mycoplasma species. This study included the immunohistochemical characterization of the pneumonic lesions of 18 goats (3-5 months old) infected with one of the following Mycoplasma species: M. mycoides ssp. mycoides, Large Colony type (goats no. 1-6), M. mycoides ssp. capri (goats no. 7-12) and M. capricolum ssp. capricolum (goats no. 13-18). Microscopically, infected animals showed a moderate broncho-interstitial pneumonia, characterized by lymphoid hyperplasia of the BALT and infiltration of mononuclear cells in the alveolar walls and airways. The main cellular type in the BALT was represented by CD3+ T lymphocytes, and the ratio of CD4+:CD8+ cells was > 2. The BALT showed large germinal centres mainly composed of IgG+ B lymphocytes, with numerous S-100+ follicular dendritic cells. The presence of follicular dendritic cells confirmed the high degree of organization of this lymphoid tissue. The immunohistochemical results showed that activated T lymphocytes, particularly in the CD4 subset, and IgG+ B cells, play a major role in the immune response of the caprine lung infected with these species of mycoplasmas.

Animals↗

PubMed2001

Human immunodeficiency virus type 1 (HIV-1) non-B subtypes are similar to HIV-1 subtype B in that coreceptor specificity is a determinant of cytopathicity in human lymphoid tissue infected ex vivo.

We sought to determine the relationship between virus-mediated CD4(+) T-lymphocyte cytopathicity and viral coreceptor preference among various human immunodeficiency virus type 1 (HIV-1) subtypes in an ex vivo-infected human lymphoid tissue model. Our data show that all R5 HIV-1 infections resulted in mild depletion of CD4(+) T lymphocytes, whereas all X4 HIV-1 infections caused severe depletion of CD4(+) T lymphocytes regardless of their subtype origin. Thus, at least for the viruses within subtypes A, B, C, and E that were tested, coreceptor specificity is a critical factor that determines the ability of HIV-1 to deplete CD4(+) T cells in human lymphoid tissue infected ex vivo.

Acquired Immunodeficiency Syndrome↗

PubMed1999

Acquired gastric mucosa-associated lymphoid tissue (MALT): a review with special emphasis on association with extragastric diseases and management problems of gastric MALT.

Mucosa-associated lymphoid tissue is absent physiologically in normal gastric mucosa, but it can develop in some pathologies (dyspepsia, celiac disease, autoimmune diseases) due to certain (Helicobacter pylori, gluten) or uncertain (viruses?) antigenic stimuli. Its importance is related to the consideration that it is the background for the development of gastric mucosa-associated lymphoid tissue (MALT) lymphoma, and its histologic progression to MALT lymphoma may be diagnosed using Isaacson's score. Monoclonal bands can be diagnosed in acquired gastric MALT as well as in gastric MALT lymphoma, but its role is unknown. To prevent development of MALT lymphoma from acquired MALT, currently anti-H. pylori treatment in all H. pylori- and MALT-positive patients is not suggested--only in patients with grade 3 of acquired MALT--due to the high risk of developing MALT lymphoma in these patients. At the same time, the etiology of gastric MALT in autoimmune extragastric diseases is not clear. Additional studies are needed to clarify this relation and its possible causes.

Autoimmune Diseases↗

PubMed1999

CD95 ligand (CD95L) in normal human lymphoid tissues: a subset of plasma cells are prominent producers of CD95L.

CD95(Fas/APO-1)-ligand (CD95L) mediates apoptosis by trimerization of the CD95 receptor on the surface of sensitive cells. In vitro studies have shown CD95L expression mainly by activated T cells and suggested a role for CD95L in the regulation of immune responses. Little is known, however, about the cellular distribution of CD95L in situ in the normal human immune system. We investigated CD95L expression in tissue sections of the thymus, lymph node, spleen, tonsil, and gastrointestinal tract using in situ hybridization and two monoclonal antibodies. In all these organs, cells expressing CD95L message and protein were scarce and comprised scattered lymphocytes, rare nonlymphoid cells, and a subset of epithelioid endothelial cells. Surprisingly, a subset of plasma cells turned out to be the most prominent producers of CD95L, matching the reports on CD95L in myeloma cells. CD95L+ plasma cells were most numerous in the mucosa-associated lymphoid tissue. This also applied to acquired mucosa-associated lymphoid tissue in chronic gastritis in which CD95L+ plasma cells were found scattered in the lamina propria. Our data suggest that plasma cells as yet may be neglected modulators of immune responses.

Antibodies, Monoclonal↗

PubMed2002

Regression of CD5-positive and Helicobacter pylori-negative mucosa-associated lymphoid tissue lymphoma of the rectum after administration of antibiotics: report of a case.

We report a case of mucosa-associated lymphoid tissue lymphoma of the rectum that regressed after antibiotics administration. A 70-year-old female complained of abdominal discomfort. Colonoscopy performed in July 1998 showed a hemispheric protrusion of the rectum, the surface of which was covered with normal rectal mucosa. Pathologic diagnosis of a biopsy specimen was low-grade mucosa-associated lymphoid tissue lymphoma. Gastroscopy showed multiple erosions of the antrum, and was negative by both culture and histology. After informed consent the patient was treated with a 14-day course of lansoprazole, amoxicillin, and clarithromycin for the eradication of. Repeat colonoscopy ten days after initiation of treatment showed that the rectal tumor had disappeared, and this was confirmed by histologic examination. There was no recurrence during 20 months of follow-up.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed1996

Identification of novel lymphoid tissues in murine intestinal mucosa where clusters of c-kit+ IL-7R+ Thy1+ lympho-hemopoietic progenitors develop.

We have revealed that about one and a half thousand tiny clusters, filled with one thousand closely packed lymphocytes, can be found throughout the murine small and large intestinal mucosa. They are located in crypt lamina propria (cryptopatches; CP) and can be first detected at 14-17 d after birth. A large fraction of lymphocytes in CP expresses c-kit, IL-7R, Thy1 and a lymphocyte function-associated antigen, LFA-1, whereas most of them remain CD3-, TCR alpha beta-, TCR gamma delta-, sIgM-, and B220-. The population size of IL-2R alpha+, HSA+ and Pgp-1+ subsets is variable (20-50%) and the composition of CD8+, Ly-1+, and CD4+ subsets is smaller but also variable (3-20%). In the small intestine, CP do not contain cells undergoing apoptosis nor cells bearing RAG-1 molecules, but do contain dendritic stromal cells bearing CD11c/CD18 molecules. The frequency of DNA replicating cells in CP is higher than that in Peyer's patches (PP), is lower than that in the thymic cortex and is almost comparable with that in the thymic medulla. The numbers of CP remain the same in aged mice (> 114 wk) but double after estrogen treatment even though the thymi are attenuated sharply in both conditions. Thus, with respect to histogenesis, lymphocyte composition and tissue level of cellular behavior, neither PP, isolated lymphoid follicles, peripheral LNs, nor thymus are identical with CP. Finally, CP are virtually absent in lamina propria of IL-7R-deficient mice that display a profound reduction in thymic and peripheral lymphoid cellularity. By contrast, CP are present in germ-free mice and in athymic (nu/nu), SCID, TCR beta x delta-/-, RAG-2-/-, PP-deficient (aly/aly), stem cell factor (Sl/Sld) and c-kit (W/Wv) mutant mice. Taking all of these results together, CP are the first identification of gut-associated murine lymphoid tissues where the generation of IL-7-dependent lympho-hematopoietic progenitors for T and/or B cell descendants may start to take place at the age of commencement of weaning.

Animals↗