Immunohistological characterization of proximal colonic lymphoid tissue in the rat

Proximal colonic lymphoid tissue (PCLT) is a lymphoid structure located in the proximal colon of the mouse and the rat. In the present investigation we studied the immunomorphology and cytology of PCLT in the rat. We also studied sites of lymphocyte proliferation using the BrdU-anti BrdU technique. Results demonstrated no evident phenotypical differences between the lymphocyte populations of PCLT and either jejunal or ileal Peyer's patches (PP). The majority of the lymphocytes within PCLT were B cells localized in follicles, which were separated from each other by interfollicular T cell areas. Germinal centers (GC), containing ED5⁺ follicular dendritic cells, are found within PCLT follicles. The T cell areas contained both MHC Class II⁺ interdigitating cells and high endothelial venules. Studies using BrdU-anti BrdU indicated that lymphocyte proliferation within PCLT taken place mainly in germinal centers. Together the data show that the organization, lymphoid constituents, and sites of lymphocyte production are very similar in PCLT and PP. We therefore conclude that PCLT in the rats is not a Bursa equivalent, but more likely a PP with some special characteristics. © 1992 Wiley-Liss, Inc.     

Immunohistological characterization of proximal colonic lymphoid tissue in the rat.

Proximal colonic lymphoid tissue (PCLT) is a lymphoid structure located in the proximal colon of the mouse and the rat. In the present investigation we studied the immunomorphology and cytology of PCLT in the rat. We also studied sites of lymphocyte proliferation using the BrdU-anti BrdU technique. Results demonstrated no evident phenotypical differences between the lymphocyte populations of PCLT and either jejunal or ileal Peyer's patches (PP). The majority of the lymphocytes within PCLT were B cells localized in follicles, which were separated from each other by interfollicular T cell areas. Germinal centers (GC), containing ED5+ follicular dendritic cells, are found within PCLT follicles. The T cell areas contained both MHC Class II+ interdigitating cells and high endothelial venules. Studies using BrdU-anti BrdU indicated that lymphocyte proliferation within PCLT takes place mainly in germinal centers. Together the data show that the organization, lymphoid constituents, and sites of lymphocyte production are very similar in PCLT and PP. We therefore conclude that PCLT in the rat is not a Bursa equivalent, but more likely a PP with some special characteristics.     

Subpopulations of lymphoid and non-lymphoid cells in bronchus-associated lymphoid tissue (BALT) of the mouse

Lymphoid and non-lymphoid subpopulations were investigated in the lung of the mouse with immunocyto-, immunohisto- and enzyme-histochemical methods. Special attention was paid to the cell populations in bronchus-associated lymphoid tissue (BALT), which is positioned between a bronchus and an artery. In BALT, discrete T- and B-cell areas can be found. The majority of the T cells belong to the L3T4+ (T-helper) subpopulation. In the T-cell area interdigitating cells can be recognized by anti-class II antibodies as well as by specific monoclonal antibodies, NLDC-145 and MIDC-8. Macrophage subpopulations can be discriminated by location, enzyme reactivity and various macrophage-specific monoclonal antibody markers. On the outer rim of BALT macrophages are recognized by the MOMA-1 and ERTR9 antibody. Macrophages dispersed in BALT can only be discriminated with the MOMA-2 antibody. The macrophage markers F4/80 and Mac-1 show no reactivity in BALT. In lung, tissue macrophages around bronchi and blood vessels are predominantly recognized by the MOMA-1 and MOMA-2 antibody, and a minor population by the ERTR9 antibody. Alveolar macrophages show heterogeneity with the MOMA-1, MOMA-2 and NLDC-145 antibody. The relationship between alveolar macrophages and antigen-presenting cells is discussed here.     

Heterogeneity of lymphoid tissue inducer cell populations present in embryonic and adult mouse lymphoid tissues

Lymphoid tissue inducer (LTi) cells have a well established role in secondary lymphoid tissue development. Here, we report on the heterogeneity of LTi cells based on their CD4 and chemokine receptor expression. The CD4⁻ LTi-cell population has a similar phenotype to the CD4⁺ population, with similar chemokine-receptor-expressing subsets. In both embryonic and adult spleen the CD4⁻ LTi-cell population is comparable as a proportion of total splenocytes to its CD4⁺ counterpart. In contrast, different proportions of CD4⁺ and CD4⁻ LTi cells are found in different lymph nodes. Both CD4⁺ and CD4⁻ LTi cells share the anatomical location and are associated with vascular cell adhesion molecule-1-positive stromal cells in spleen and lymph nodes. The numbers of both CD4⁺ and CD4⁻ LTi cells in adult spleen are augmented in the presence of B cells. With the exception of CD4, there is a strong correlation coefficient (0·89) for gene expression between the two populations. Polymerase chain reaction analysis of individual CD4⁺ and CD4⁻ LTi cells shows that a similar proportion in embryonic and adult spleen co-expressed both CXCR5 and CCR7 or CXCR5 alone: 84·6% for adult CD4⁺ and 87·6% for adult CD4⁻; 95·3% for embryonic CD4⁺ and 91·5% for embryonic CD4⁻. Consistently fewer CCR7 single-positive cells were found in the CD4⁺ and CD4⁻ fractions in the embryo.     

Characterization of tumor-infiltrating T lymphocytes in B-cell lymphomas of mucosa-associated lymphoid tissue.

B-cell lymphomas of mucosa-associated lymphoid tissue invariably contain large numbers of reactive tumor-infiltrating T cells. In the stomach, these lymphomas develop secondary to Helicobacter pylori infection, and clinical and in vitro studies have shown that their growth depends on help provided by H. pylori-specific T cells. In this study we characterized tumor-infiltrating T cells in low- and high-grade B-cell lymphomas of mucosa-associated lymphoid tissue using immunohistochemistry. In most cases, CD4+ T cells dominated and almost all T cells were CD45RO+ memory cells. In 11 of 13 cases studied, the proliferating T cells were CD4+ and no proliferation was observed in the CD8+ subset. In low-grade lymphomas, between 7 and 24% of T cells expressed CD40L whereas no CD40L expression was observed in the majority of high-grade tumors. Examination of homing receptor profile showed that both alpha 4 beta 7 integrin+ and L-selectin+ T cells were present. Examination of T cell diversity by a panel of antibodies against different T-cell receptor V beta regions and by analysis of T-cell receptor genes using polymerase chain reaction suggested that the T cells in these tumors were polyclonal. These results show that low-grade B-cell lymphomas of mucosa-associated lymphoid tissue contain a significant population of activated helper T cells that may be important in supporting tumor growth.     

The presence of specialized epithelial cells on the bronchus-associated lymphoid tissue (BALT) in the mouse

The aggregation of lymphoid cells in the bronchial mucosa has been named the bronchus-associated lymphoid tissue (BALT) and investigated in comparison with the gut-associated lymphoid tissue (GALT). To elucidate precisely the structure and function of the BALT, the present study examined the age-related change in the mouse BALT by light microscopy. We also observed the characteristics of the overlying epithelium, especially the lectin-binding properties of the epithelial cells, by the combined use of light microscopy (LM), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). By LM, lymphoid aggregates were not recognizable in the bronchial mucosa of young (8-10 week-old) mice, while they were commonly found at the second to fourth branching portions of the bronchial tree in older (32-40 week-old) mice. The epithelium overlying the lymphoid aggregates of the mature mice often contained a large number of mononuclear cells. Lectin cytochemistry revealed that UEA1 (Ulex europaeus agglutinin 1) positive cells were not only restricted to the overlying epithelium of the BALT in the older mice but also found in a cell group in the mucous epithelium at the branching portions in the young mice. Comparison between the LM and SEM images of the UEA1-stained whole mount specimens clarified the surface morphology of the lectin-stained epithelial cells, showing them to be non-ciliated cells with a large number of short microvillous projections on the apical surface. TEM studies further demonstrated that the UEA1 reaction products appeared on the plasma membrane of the non-ciliated cells which often enfolded lymphocytes in the old mice. Latex microbeads, which were administrated intratracheally, were selectively taken up by the UEA1-positive cells of the BALT. These results indicate that the mouse BALT has specialized epithelial cells similar to the UEA1 positive M cells in the GALT and probably functions as a part of the mucosal immune system. This study also showed the possibility that the UEA1 positive cells appear in the mucous epithelium before the formation of the BALT.     

Mucosa-associated lymphoid tissue lymphoma of the esophagus coexistent with bronchus-associated lymphoid tissue lymphoma of the lung

Non-Hodgkin's lymphoma very rarely involves the esophagus, occurring in less than 1% of patients with gastrointestinal lymphoma. A few cases of mucosa-associated lymphoid tissue (MALT) lymphoma of the esophagus have been reported in the English literature. To our knowledge, there has been no report of MALT lymphoma of the esophagus coexistent with bronchus-associated lymphoid tissue lymphoma (BALT) of the lung. This report details the radiological and clinical findings of this first concurrent case.     

Characterization of ovine nasal-associated lymphoid tissue and identification of M cells in the overlying follicle-associated epithelium.

The distribution of mucosal lymphoid nodules in the ovine nasopharyngeal tract was studied by an acetic acid fixation technique. Nodules, which were concentrated just posterior to the opening of the Eustachian tube, were excised and examined by light microscopy, and scanning and transmission electron microscopy. Immunohistochemical examination revealed that each lymphoid structure consisted of follicles containing discrete B- and T-cell areas, characteristic of a mucosal inductive site of the mucosa-associated lymphoid tissue (MALT). Electron microscopy revealed that specialized epithelial cells, displaying features characteristic of M cells, were present in the follicle-associated epithelium (FAE) that covered the lymphoid nodules. These cells had sparse irregular microvilli and were closely associated with lymphocytes in the underlying tissue. These findings suggest that targeting the nasopharyngeal region may provide a practical and effective route for the stimulation of protective mucosal immune responses.     

Reaction of different functional zones in mouse thymus and spleen lymphoid tissue to γ-irradiation

It is shown that immune organs respond to single γ-radiation of 6.9 Gy in a cyclic manner. Acute reaction characterized by spontaneous lymphocyte lysis in the thymus and spleen develops on day 1 postirradiation and takes 3 and 7 days, respectively. This is followed by enhancement of thymocyte mitotic activity and migration of young cells to the thymic cortex and splenic lymphoid tissue. Twenty-one day postirradiation lymphoid cell populations in the thymus and spleen recover to 70–90 and 55–70%, respectively. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 125, No. 4, pp. 381–384, April, 1998     

黏膜相关淋巴组织淋巴瘤

在呼吸道、消化道、泌尿生殖道黏膜及黏膜下存在无结构、散在的淋巴细胞。有结构的黏膜相关淋巴组织主要存在于回肠末端及支气管黏膜下。其最具特征的结构为Peyer斑（Peyer’s patches,1667年首先由Peyer描述而得名）。有结构的黏膜相关淋巴组织与淋巴结的淋巴组织结构相似,但无包膜。单个Peyer斑呈卵圆形,由生发中心、帽区及宽阔的边缘带B细胞构成。其外围为相邻的副皮质区样的T细胞区。边缘区的B细胞可进入覆盖Peyer斑的圆顶区上皮内（这些上皮内的B细胞与小肠其他部位上皮内的T细胞有别）。此外,固有膜内的浆细胞也是黏膜相关淋巴组织的一个组成成分。概括起来,     

鼻粘膜相关淋巴组织的研究进展

鼠类鼻粘膜相关淋巴组织是人类的Waldeyer's环的对应组织，为鼻腔免疫后诱导产生抗原特异性免疫反应的部位。最近发现特别在上呼吸道和生殖道鼻免疫比胃肠道免疫更有效地诱导系统和多处粘膜局部的免疫反应，而引起广泛关注。本文综述鼻粘膜相关淋巴组织的结构与其它粘膜相关淋巴组织的异同及其在局部和系统免疫中的作用等。     

Histopathology of mucosa-associated lymphoid tissue

Mucosa-associated lymphoid tissue (MALT) is a generalized term incorporating a disseminated collection of lymphoid tissues in multiple sites throughout the body. MALT sites that have been/are primarily studied include bronchus-associated lymphoid tissue (BALT), gut-associated lymphoid tissue (GALT), and nasopharynx-associated lymphoid tissue (NALT). Since MALT sites are often under-sampled in conventional toxicity studies, MALT lesions have not been extensively documented in these lymphoid effector sites. Lesions of the nasopharyngeal lymphoid tissue and Peyer's patches include degeneration, inflammation, and both primary and metastatic neoplasia.     

Heparin-induced hyperplasia of lymphoid tissue

Experiments on newborn and sexually mature mice and rats showed that repeated injection of heparin leads to an increase both in the number of lymphocytes in the thymus and spleen and in the number of hematopoietic stem cells forming endogenous colonies in the spleen. The lymphoid tissue and the pool of colony-forming units are conjecturally under the regulatory influence of the adrenocortical hormones and of the product of the mast cells-heparin.     

Mucosa-associated lymphoid tissue lymphoma in conjunctiva

A case of primary mucosa-associated lymphoid tissue (MALT) lymphoma (marginal zone B-cell lymphoma of MALT according to WHO classification) in conjunctiva, which presented as a slowly growing salmon-colored mass at limbus of left eye is reported. Histological examination revealed a diffuse low-grade lymphoma. Immunohistochemical analysis using monoclonal antibodies showed that the tumor cells are leukocyte common antigen (CD45)+, CD20+, CD3-, CD5-, CD10- and CD43-, which confirmed the B-cell lineage of lymphoma. The case is being reported for its rarity and clinical importance of recognizing such cases because of excellent prognosis.     

Studies of intestinal lymphoid tissue

Summary Peroral jejunal mucosae from 32 patients with untreated DH were quantitated by computerized image-analysis in terms of surface (villous) and crypt epithelial volumes and their corresponding lymphoid infiltrates, together with lamina propria volumes, neutrophils, mast cells and basophils. Three distinctive patterns of mucosal abnormality were identified: (a) the infiltrative lesion in which normal villus epithelium was infiltrated by small, non-mitotic lymphocytes: (b) the hyperplastic type, in which crypt hyperplasia and hypertrophy together with lymphoid infiltration of crypt epithelium was additional to the infiltrative lesion, and in which lamina propria was swollen and contained modest neutrophilic and basophilic infiltration: and (c) the destructive lesion, identical to the classic celiac sprue appearances with effacement of villi, crypt hypertrophy and more intensive polymorph infiltration of lamina propria. These progressive lesions parallel those seen in experimental graft-versus-host reactions, so that the entire spectrum of changes described here in DH appear consistent with a cell-mediated mucosal response to gluten. The extent of mucosal abnormality was unrelated to individual HLA status.Supported by the Medical Research Council, England     

Studies of intestinal lymphoid tissue

Summary A proportion of epithelial lymphocytes in various mammalian species is characterised by cells containing cytoplasmic granules. We have studied the total number of granular lymphocytes within surface and crypt epithelium of jejunal mucosae (per 10⁴ µm² muscularis mucosae) from six groups of subjects, comprising (i) young healthy volunteers (ii) family relatives of known coeliac patients, patients with gastrointestinal disorders associated with either (iii) normal or (iv) flat mucosae, and groups of (v) untreated and (vi) treated patients with coeliac disease. There was no difference in the absolute number of gEL between the three control groups with normal mucosal architecture, the proportion of granular to total EL per unit of tissue varying between 30–40% . In untreated coeliac mucosae, there was a significantly increased population of gEL, compared with the same control groups (p<0.001): the ratio of granular to total EL approximated 65%, and did not differ from flat-control mucosae in which the proportion of gEL was 55%. On withdrawal of gluten, the absolute number of gEL fell significantly in comparison with the untreated coeliac group (p< 0.05). To further evaluate the effect of gluten challenge, granular lymphocytes were monitored during a five-day period in groups of treated coeliac patients orally challenged with increasing doses (500–3000 mg) of a peptic-tryptic digest of gluten. A significant rise in the absolute number of granular lymphocytes occurred at 12 h, but without any deterioration in mucosal architecture.Supported by the Medical Research Council, Great Britain