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PubMed2004

Secondary lymphoid tissue chemokine (CCL21) is upregulated in allergic contact dermatitis.

Chemokines are important players in the development of allergic contact dermatitis (ACD). The participation of secondary lymphoid tissue chemokine (CCL21) is essential in the induction of the disease due to its expression in lymphatic vessels and in secondary lymphoid organs. Since there is no information about its participation during the effector phase of ACD, we studied this chemokine in patients already diagnosed with ACD, who were challenged with the relevant positive and negative (control) antigens. All patients showed a specific antigen-induced immune response characterized by early expression of inflammatory markers in blood endothelial cells followed by dermal accumulation of mononuclear cells with an important increase in infiltration of CXCR3+ but not of CCR7+ cells. In situ hybridization and immunohistochemistry showed low levels of CCL21 in lymphatic vessels at 2 h, whereas they were significantly increased at 10 and 48 h in all positive patch tests. In contrast, very low expression of this chemokine was observed in skin biopsies from the control site at 48 h. In addition, Langerin+ cells, which were present in dermis from positive patch tests at 2 h, were diminished in number at 10 and 48 h, but a significant number of those cells was still present in dermal areas of the control site at 48 h. We demonstrate for the first time that CCL21, a constitutively expressed chemokine, is strongly upregulated in human lymphatic vessels during a Th1/Tc1 allergic inflammatory response. This can provide the signal required for CCR7+ cells to leave the skin through CCL21-positive lymphatic vessels.

Adult↗
PubMed1988

Depletion of bronchus-associated lymphoid tissue associated with lung allograft rejection.

Pulmonary infections remain one of the major complications of lung transplantation. The bronchus-associated lymphoid tissue (BALT) forms a local immune system that normally protects the lung from infection. The effects of lung transplantation and lung allograft rejection on the BALT were examined using immunoperoxidase techniques. The BALT was evaluated by quantifying the number of immunoglobulin-bearing plasma cells in the lamina propria of sections of trachea and mainstem bronchus. Sections of donor mainstem bronchus from 2 patients with allograft rejection were compared with sections of native trachea from these same patients, and with sections of mainstem bronchus from 2 transplanted lungs without rejection and 20 controls. Lung allografts from the 2 patients with rejection had a marked depletion of submucosal IgA-bearing and IgG-bearing plasma cells. Two sets of transplanted lungs without evidence of rejection showed only a mild reduction of the BALT. The depletion of BALT associated with allograft rejection may contribute to the increased incidence of pulmonary infections seen in these patients.

Bronchi↗
PubMed1999

Breakpoints of the t(11;18)(q21;q21) in mucosa-associated lymphoid tissue (MALT) lymphoma lie within or near the previously undescribed gene MALT1 in chromosome 18.

Lymphomas arising in mucosa-associated lymphoid tissue (MALT) are indolent B-cell tumors that have a predilection for epithelial sites and often develop in a setting of chronic inflammation or autoimmunity. As many as 50% of low-grade MALT lymphomas contain an (11;18)(q21; q21) chromosomal translocation. Using fluorescence in situ hybridization, we have analyzed the position of recombination within chromosome 18 DNA in three examples of MALT lymphoma bearing this translocation. In all three cases, the breakpoint maps to DNA in BAC b357H2, covering about 150 kb of sequence. A previously undescribed, ubiquitously expressed gene, which we refer to as MALT1, was identified within this sequence and was found to be broken in one case for which we have definitively located the position of recombination between chromosomes 18 and 11. The sequence of this gene indicates the presence of two immunoglobulin-like C2 domains and a region of partial homology to caspases, suggesting a possible role for MALT1 in the regulation of apoptosis.

Amino Acid Sequence↗
PubMed1978

Feline panleukopenia. III. Development of lesions in the lymphoid tissues.

Germfree and specific pathogen-free cats were inoculated with feline panleukopenia virus. Cats were necropsied 2 to 6 days after inoculation and tissues from the thymus, lymph nodes and spleen taken for histological and immunofluorescence studies. Necrosis of lymphoid cells in the thymic cortex began 3 days after inoculation and continued for 5 to 6 days after inoculation when the thymus was nearly depleted of lymphocytes. Immunofluorescence studies showed the lesions to be caused by virus. There was gross and histological involution of the thymus in both germfree and specific pathogen-free cats. The lymph nodes and spleen of uninoculated germfree cats looked "inactive" and lacked well developed lymphoid follicles and paracortical areas. In both germfree and specific pathogen-free cats there was necrosis in both follicular and paracortical areas of the lymph nodes and follicular and periarteriolar areas of the spleen 3 to 4 days after inoculation. Immunofluorescence showed these areas had virus infection. By 5 to 6 days after inoculation, these areas were populated by many lymphoblastoic cells. Even though significant destruction of lymphoid cells occurred, subsequently, in cats that develop mild clinical illness, these lymphoid tissues seemed stimulated rather than depleted of lymphocytes.

Animals↗
PubMed2006

Distinct comparative genomic hybridisation profiles in gastric mucosa-associated lymphoid tissue lymphomas with and without t(11;18)(q21;q21).

t(11;18)(q21;q21) occurs specifically in mucosa-associated lymphoid tissue (MALT) lymphoma and the translocation generates a functional API2-MALT1 fusion product that activates nuclear factor (NF)kappaB. t(11;18) positive lymphomas usually lack the chromosomal aberrations and microsatellite alterations frequently seen in the translocation-negative MALT lymphomas. To further understand their genetic differences, we investigated gastric MALT lymphomas with and without t(11;18) by comparative genomic hybridisation. In general, both chromosomal gains and losses were far more frequent in t(11;18)-negative (median = 3.4 imbalances) than t(11;18)-positive cases (median = 1.6 imbalances), with gains being more frequent than losses. Recurrent chromosomal gains involving whole or major parts of a chromosome were seen for chromosomes 3, 12, 18 and 22 (23%, 19%, 19% and 27% respectively). Discrete recurrent chromosomal gains were found at 9q34 (11/26 = 42%). Bioinformatic analysis of genes mapping to 9q34 revealed potential targets. Among them, TRAF2 and CARD9 are known interaction partners of BCL10, playing a role in NFkappaB activation. Interphase fluorescent in situ hybridisation confirmed genomic gain of the TRAF2, CARD9 and MALT1 loci in 5/6 and 2/2 cases showing chromosomal gains at 9q34 and 18q21 respectively. The results further highlight the genetic difference between MALT lymphomas with and without t(11;18). Moreover, our findings suggest that genomic gain of genes that modulate NFkappaB activation, such as MALT1, TRAF2 and CARD9, may play a role in the pathogenesis of the translocation-negative MALT lymphoma.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Primary low-grade B-cell lymphoma of mucosa-associated lymphoid tissue type arising in the urinary bladder: report of 4 cases with molecular genetic analysis.

CONTEXT: Primary lymphoma of the urinary bladder is rare. Only 84 cases have been reported in the English literature to date, and none of these cases has had molecular confirmation of clonal immunoglobulin gene rearrangement. OBJECTIVES: To review all cases with primary urinary bladder lymphoma in our records, to classify them using the REAL classification, to confirm their immunophenotype and genotype, and to determine their outcome. DESIGN: We identified 4 cases of primary urinary bladder lymphoma in our medical records from a 30-year period. Immunohistochemical detection of immunoglobulin light chains and molecular analysis of immunoglobulin heavy-chain genes using the polymerase chain reaction were performed on paraffin-embedded material. RESULTS: All patients were older than 60 years. The male-female ratio was 1:3. All patients had a history of chronic cystitis. Histologic features of mucosa-associated lymphoid tissue lymphoma with centrocyte-like cells, plasmacytoid B cells, or both were observed in all cases. Monoclonality of B cells was demonstrated by immunohistochemistry, polymerase chain reaction, or both methods in every case. All patients presented with stage IAE disease, were treated with radiotherapy alone, and have been in continuous complete remission for 2 to 13 years. CONCLUSIONS: Primary bladder lymphomas are usually of low-grade mucosa-associated lymphoid tissue type. They are more common in females and are associated with a history of chronic cystitis. Lymphoepithelial lesions are seen only in association with areas of cystitis glandularis. B-cell clonality is readily demonstrable by immunohistochemistry and/or polymerase chain reaction analysis. Local radiotherapy appears to confer long-term control.

Aged↗
PubMed2006

CD4 and MHC-I downregulation are conserved in primary HIV-1 Nef alleles from brain and lymphoid tissues, but Pak2 activation is highly variable.

HIV-1 compartmentalization in the CNS has been demonstrated for gag, pol, and env genes. However, little is known about tissue compartmentalization of nef genes and their functional characteristics in brain. We have cloned 97 nef genes and characterized 10 Nef proteins from autopsy brain and lymphoid tissues from 2 patients with AIDS and HIV-1-associated dementia. Distinct compartmentalization of brain versus lymphoid nef genes was demonstrated within each patient. CD4 and MHC-I downregulation were conserved in all tissue-derived Nefs. However, MHC-I downregulation by brain-derived Nefs was weaker than downregulation by lymphoid-derived Nefs. The motifs KEEE- or EKEE- at the PACS-1 binding site represented brain-specific signature patterns in these 2 patients and contributed to the reduced MHC-I downregulation activity of brain-derived Nefs from these patients. Pak2 association was highly variable in Nefs from both patients. Three of 10 tissue-derived Nefs coimmunoprecipitated activated Pak2, with strong association demonstrated for only 2 Nefs. The ability of Nef to associate with activated Pak2 did not correlate with brain or lymphoid tissue origin. Nef genes from viruses isolated from brain by coculture with PBMC were not closely related to sequences amplified directly from brain tissue, suggesting that viral selection or adaptation occurred during coculture. This study of tissue-derived HIV-1 Nefs demonstrates that CD4 and MHC-I downregulation are highly conserved Nef functions, while Pak2 association is variable in late stage AIDS patients.

AIDS Dementia Complex↗
PubMed1991

Occluding junctions in the epithelia of the gut-associated lymphoid tissue (GALT) of the rabbit ileum and caecum.

The zonulae occludentes of the dome epithelia and adjacent non-dome epithelia in four locations of the gut-associated lymphoid tissue (GALT) in the rabbit ileum and caecum (Peyer's patches, sacculus rotundus, caecal lymphoid patches, appendix) were studied in freeze-fracture replicas. In all locations the zonulae occludentes of the dome epithelium are composed of more junctional strands than in the corresponding non-dome epithelium. In the dome epithelia of Peyer's and caecal lymphoid patches the zonulae occludentes show considerable structural variation; the number of superimposed strands is approximately 10 (range 5-18). In the dome epithelia of sacculus rotundus and appendix, in addition to zonulae occludentes, extended networks of junctional strands (fasciae occludentes) are present particularly between M-cells and enterocytes. The zonulae occludentes consist of approximately 8 to 9 (range 5-15) superimposed strands; the fasciae occludentes extend up to a depth of 20 microns on the lateral membranes. The presence of the fasciae occludentes correlates with the appearance of regularly shaped clusters of lymphocytes, which are most developed in the dome epithelia of sacculus rotundus and appendix. These results suggest (1) that in contrast to the dome epithelia of Peyer's and caecal lymphoid patches those of sacculus rotundus and appendix are compartmentalized, and (2) that the mobility of lymphocytes and diffusion of antigens in the dome epithelia of sacculus rotundus and appendix is restricted.

Animals↗
PubMed2006

Cutting edge: Uniqueness of lymphoid chemokine requirement for the initiation and maturation of nasopharynx-associated lymphoid tissue organogenesis.

CD3(-)CD4(+)CD45(+) inducer cells are required for the initiation of mucosa-associated organogenesis of both nasopharynx-associated lymphoid tissues (NALT) and Peyer's patches (PP) in the aerodigestive tract. CXCL13(-/-) mice and mice carrying the paucity of lymph node T cell (plt) mutation and lacking expression of CCL19 and CCL21 accumulate CD3(-)CD4(+)CD45(+) cells at the site of NALT but not of PP genesis. Although NALT was observed to develop in adult CXCL13(-/-) and plt/plt mice, the formation of germinal centers in CXCL13(-/-) mice was affected, and their population of B cells was much lower than in the NALT of CXCL13(+/-) mice. Similarly, fewer T cells were observed in the NALT of plt/plt mice than in control mice. These findings indicate that the initiation of NALT organogenesis is independent of CXCL13, CCL19, and CCL21. However, the expression of these lymphoid chemokines is essential for the maturation of NALT microarchitecture.

Animals↗
PubMed1987

Modification of caecal lymphoid tissue and relationship to granuloma formation in sporadic ileocaecal tuberculosis.

The histopathology of eight cases of sporadic ileocaecal tuberculosis is described with particular reference to caecal lymphoid tissue. Adjacent to areas of ulceration in all cases there was an increase in lymphoglandular complexes (LGC) and proliferation of paravascular lymphoid aggregates deeper in the gut wall. Early and fully-developed granulomas were present in locations comparable to LGC and lymphoid aggregates. Immunocytochemical staining of paraffin sections with monoclonal antibodies UCHL1 (T-lymphocyte membrane antigen) and LN-1, LN-2 and LN-3 (B-lymphocyte and Ia antigens) showed that central cells in LGC and lymphoid aggregates stained like follicular centre B-lymphocytes. Both LGC and lymphoid aggregates had a distinct peripheral rim of cells staining as T-lymphocytes, but LN-2 and LN-3 also stained scattered peripheral cells, some of which were recognizable as interdigitating reticulum cells. Most lymphocytes within and around granulomas stained as T-lymphocytes. In lymph nodes, granulomas appeared to occur first at the periphery of, and later to efface, cortical follicles. Lymph node compartments showed the expected T- and B-zonation, and lymphocytes associated with granulomas stained as in caecal granulomas. Our observations suggest that LGC are sites of mycobacterial antigen sampling, of T-lymphocyte and macrophage activation, and of (potential) granuloma formation in ileocaecal tuberculosis. Lymphoid aggregates deeper in the gut wall probably subserve a similar function during extension of the lesion. The location of both LGC and lymphoid aggregates beside lymphatics is suited to the transfer of their cellular constituents throughout the gut and to regional lymph nodes.

Aged↗
PubMed2003

Distinct gene expression profiles characterize the histopathological stages of disease in Helicobacter-induced mucosa-associated lymphoid tissue lymphoma.

Long-term colonization of humans with Helicobacter pylori can cause the development of gastric B cell mucosa-associated lymphoid tissue lymphoma, yet little is known about the sequence of molecular steps that accompany disease progression. We used microarray analysis and laser microdissection to identify gene expression profiles characteristic and predictive of the various histopathological stages in a mouse model of the disease. The initial step in lymphoma development is marked by infiltration of reactive lymphocytes into the stomach and the launching of a mucosal immune response. Our analysis uncovered molecular markers of both of these processes, including genes coding for the immunoglobulins and the small proline-rich protein Sprr 2A. The subsequent step is characterized histologically by the antigen-driven proliferation and aggregation of B cells and the gradual appearance of lymphoepithelial lesions. In tissues of this stage, we observed increased expression of genes previously associated with malignancy, including the laminin receptor-1 and the multidrug-resistance channel MDR-1. Finally, we found that the transition to destructive lymphoepithelial lesions and malignant lymphoma is marked by an increase in transcription of a single gene encoding calgranulin AMrp-8.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1993

Immunoglobulin specificity of low grade B cell gastrointestinal lymphoma of mucosa-associated lymphoid tissue (MALT) type.

The specificity of the tumor cell immunoglobulin in three cases of low grade B cell gastrointestinal mucosa-associated lymphoid tissue (MALT) lymphoma has been studied. Using anti-idiotypic antibodies to detect the reactivity of tumor immunoglobulin in tissue sections from the patients and other individuals, we observed specificity for normal tissue components in all three cases studied. Reactivity in one case was with follicular dendritic cells, in the second case with a novel antigen on mucosal post capillary venules, and, in the third case, a broad pattern of reactivity was observed. This study suggests that autoimmunity may play a role in the pathogenesis of gastric lymphoma.

Antibodies, Anti-Idiotypic↗
PubMed2004

Bronchial-associated lymphoid tissue lymphoma: a clinical study of a rare disease.

Bronchial-associated lymphoid tissue (BALT) lymphoma is a distinct subgroup of low-grade B-cell extranodal non-Hodgkin's lymphoma, classified as marginal-zone lymphoma. This study was performed in order to assess the natural history of this rare entity. We evaluated retrospectively the clinical data of 22 patients with biopsy-proven BALT lymphoma at two tertiary-care institutions from 1996 to 2002. Immunophenotyping was done to confirm the abnormal populations of B-lymphoid cells in all cases, and clonality was determined by flow cytometry or molecular studies. There were 11 men and 11 women in the sample, median age 61 years (range 21-80 years); nine were asymptomatic at diagnosis. All 13 symptomatic patients had non-specific pulmonary complaints. On computed tomographic examination of the chest, 11 patients had bilateral disease, 12 had lung nodules, and 10 had a mass or air-space consolidation. In all but one case the disease was localised to the lung at diagnosis and none had peripheral blood or bone marrow involvement. Out of 22 patients, 20 received treatment in various combinations, 12 had chemotherapy and/or rituximab, six had surgery, and two received radiation therapy as primary treatment. A complete response (CR) was achieved in nine patients and a partial response was obtained in 10 patients. Seven of 10 patients who had unilateral disease achieved a CR. The estimated progression-free survival was 53 months. All patients were alive during the median follow-up period of 36 months (range 12-76 months). It appears that BALT lymphoma tends to be localised to lung at the time of diagnosis, responds well to local or systemic therapy, and has a favourable prognosis.

Adult↗
PubMed1995

Bronchus-associated lymphoid tissue (BALT) in the lungs of children who had died from sudden infant death syndrome and other causes.

BACKGROUND: Bronchus-associated lymphoid tissue (BALT) is well characterised in rabbits and rats. In humans, however, it does not seem to be present in the healthy adult lung, although it can develop after certain microbial stimulation. METHODS: In the present study a consecutive series of lungs from 88 children who had died of sudden infant death syndrome (SIDS) and 34 control cases of comparable age were examined for the presence of BALT. RESULTS: BALT was present in 36.4% of the patients who had died of SIDS and in 44.1% of the control cases. The probability of finding BALT increased with age, with similar kinetics in both groups. CONCLUSIONS: Future studies need to define when and at what rate BALT disappears as children get older. In young children BALT may act as an entry site for antigens to initiate an immune response, as is well documented for the gut-associated lymphoid system.

Age Factors↗
PubMed2005

Effector lymphoid tissue and its crucial role in protective immunity.

It is often argued that T cell-mediated immunity to secondary infection is dependent on the 'accelerated' responses of memory T cells in lymph nodes. However, new evidence points to a crucial role for effector memory T cells, which are resident in peripheral tissues, in immune protection. These T cells, which reside in peripheral tissues, are not necessarily bound by an anatomical structure and can be present at many sites. Collectively, they represent a third functional tissue of the immune system, uniquely specialized to mediate protective immunity. We propose that the paradigm 'effector lymphoid tissue' needs to be articulated and developed as a focus of new research to describe and understand the unique role this tissue has in protective immunity.

Animals↗
PubMed2006

NK cells of human secondary lymphoid tissues enhance T cell polarization via IFN-gamma secretion.

Human secondary lymphoid tissues harbor NK cells that predominantly secrete cytokines in response to activation. Here, we demonstrate that these immunoregulatory NK cells assist in the Th1 polarization of primary immune responses, induced by dendritic cells. Tonsilar, but not peripheral blood NK cells enhanced the expansion of IFN-gamma-producing CD4+ T cells via their superior ability to produce IFN-gamma. Addition of IFN-gamma increased Th1 polarization while antibody blocking of this cytokine abolished NK cell-dependent Th1 polarization. Our data suggest that NK cells in secondary lymphoid organs assist priming of Th1 cells via cytokine secretion and this effect should be harnessed during vaccination against viruses and tumors.

Cell Differentiation↗
PubMed1993

Increases in protein phosphatase 2B activity in lymphoid tissues and T-lymphocytes of autoimmune MRL/MpJ-lpr/lpr mice.

The assay conditions for protein phosphatase 2B (PP2B) in crude extracts from mouse lymphoid tissues and lymphocytes were extensively investigated. Under the conditions elucidated, the PP2B activity was measured in autoimmune-prone MRL/MpJ-lpr/lpr mice (MRL/lpr mice) and two control strains, MRL/MpJ- +/+ mice (MRL/+/+ mice) and C3H/HeJ mice. In the control mice, PP2B activity was distinctly higher in spleen and thymus than brain and liver. PP2B activity was further elevated in spleen of MRL/lpr mice than in the controls. Furthermore, we observed a specific increase in PP2B activity in T lymphocytes from MRL/lpr mice as compared with in those from control mice. On the other hand, no alteration was observed in PP2B activity in B lymphocytes. These results suggest the involvement of PP2B in the abnormal signal transduction and proliferation of T lymphocytes in MRL/lpr mice.

Animals↗