Rabbit tonsil-associated M-cells express cytokeratin 20 and take up particulate antigen.

M-cells are believed to play a pivotal role in initiation of the immune response. These cells, located in the epithelia that overlie mucosal lymphoid follicles, are responsible for the active uptake of particulate antigens and for their translocation to the underlying lymphoid tissue. The identification of reliable markers for M-cells is therefore extremely important for the study of the initial steps that lead to the immune response. For this purpose, we studied cytokeratin 20 (CK20) expression in the epithelium of rabbit palatine tonsils by immunofluorescence, confocal microscopy, and Western blotting. CK20+ cells were observed in all rabbit palatine tonsils examined. By Western blotting, one CK20-immunoreactive band was identified at 46 kD on samples of proteins from the intermediate filament-enriched cytoskeletal fraction of tonsil epithelium. Double labeling of CK20+ cells with cell-specific markers confirmed that such cells were actually M-cells. Moreover, CK20+ M-cells displayed a mature phenotype (they formed pockets harboring lymphoid cells) and were functionally competent because they could take up particulate antigens from the pharyngeal lumen. We conclude that CK20 is an M-cell marker for rabbit palatine tonsils. Moreover, we can hypothesize the use of M-cells as a possible site for antigen delivery of particle-based vaccines.     

Cathepsin E in follicle associated epithelium of intestine and tonsils: localization to M cells and possible role in antigen processing

A specific rabbit anti-human serum was used selectively to localize the aspartic proteinase cathepsin E to follicle associated epithelium (FAE) of human and rat intestine, including jejunum, ileum, appendix, colon and rectum, as well as of human palatine, pharyngeal and lingual tonsils. Coexpression of class II histocompatibility antigen HLA-DR antigen has been observed in some of the cathepsin E-positive epithelial cells. In addition, cathepsin E has been detected in a few mononuclear cells of intestinal lymphoid structures and tonsils resembling interdigitating reticulum cells of lymph nodes. Another aspartic proteinase, cathepsin D, has been found to be poorly represented in FAE and intensely expressed by macrophages. Electron immunocytochemistry localized cathepsin E to endosomal vesicles and endoplasmic reticulum of M cells in rat and human ileum as well as of M-like cells in human palatine tonsil. The results suggest a possible role of endosomal cathepsin E in the processing of macromolecules and microorganisms transported by M cells and related epithelial cells to mucosal associated lymphoid tissue (MALT).     

Ultrastructural identification and distribution of the adhesion molecules ICAM-1 and LFA-1 in the vascular and extravascular compartments of the human palatine tonsil

Summary Immunohistological analysis of sections prepared from human palatine tonsils revealed marked differences in the distribution of the adhesion molecule, leucocyte function antigen-1 (LFA-1) and its counter receptor, intercellular adhesion molecule-1 (ICAM-1). Light microscopy showed that LFA-1 was restricted to the leucocytes, particularly the lymphocytes. In contrast, staining of ICAM-1 was predominantly confined to the vascular endothelium with the greatest expression seen on the morphologically distinct high endothelial venules in the parafollicular areas; these are the sites that appear to support lymphocyte migration. Electron microscopy revealed that ICAM-1 was present on the luminal and lateral surfaces of the high endothelium and absent from the abluminal surface supported by basal lamina. The ICAM-1 was also absent from those surfaces of the endothelium that were in close contact with intravascular lymphocytes. Other cells stained by the anti-ICM-1 antibody included dendritic cells, plasma cells and epithelial cells in the reticulated crypt epithelium and in the upper strata of the non-keratinised stratified squamous epithelium. The high expression of LFA-1 was most prominent on lymphocytes, low on antigen-presenting cells and activated lymphoid cells, and not detectable on plasma cells, epithelial and endothelial cells. We propose that LFA-1/ICAM-1 binding participates in mediating the transendothelial migration of lymphocytes across the high endothelial venules of palatine tonsil.     

Morphofunctional Organization of Lymphoepithelial Organs of the Human Pharynx

We present the current concepts of morphofunctional organization of the lymphoepithelial organs in the human pharynx based on the published data and authors" results. Functional compartmentation of palatine and pharyngeal tonsils is considered, which reflects cooperative cell interactions in the immune response; B- and T-areas have been structurally isolated and functionally substantiated. A special attention is paid to the fine structure of cryptal epithelium and its interactions with lymphoid cells infiltrating the epithelial sheet: lymphoepithelial symbiosis. Attention is also paid to structural homology of the lymphoepithelial compartment of palatine tonsils and thymus. The problem concerns the place of lymphoepithelial organs in hierarchy of the immune system as secondary organs with their own immunoregulatory area and having the functions of a regional center controlling the mucosal immunity.     

Expression of intermediate filament proteins in fetal and adult human lung tissues

The expression patterns of intermediate filament proteins in fetal and normal or nonpathological adult human lung tissues are described using (chain-specific) monoclonal antibodies. In early stages of development (9-10 weeks and 25 weeks of gestation) only so-called simple cytokeratins such as cytokeratins 7 (minor amounts). 8, 18 and 19 are detected in bronchial epithelial cells. At later stages of development, the cytokeratin expression patterns become more complex. The number of bronchial cells positive for cytokeratin 7 increases, but basal cells in the bronchial epithelium remain negative. These latter cells show, however, expression of cytokeratin 14 in the third trimester of gestation. Developing alveolar epithelial cells express cytokeratins 7, 8, 18 and 19. In adult human bronchial epithelium cytokeratins 4 (varying amounts), 7, 8, 13 (minor amounts), 14, 18 and 19 can be detected, with the main expression of cytokeratins 7, 8, and 18 in columnar cells and the main expression of cytokeratin 14 in basal cells. Vimentin is detected in all mesenchymal tissues. In addition, fetal lung expresses vimentin in bronchial epithelium, however, to a lesser extent with increasing age, resulting in the expression of vimentin in only few scattered bronchial cells at birth. Also in adult bronchial epithelium the expression of vimentin is noticed in part of the basal and columnar epithelial cells. Desmin filaments, present in smooth muscle cells of the lung, appear to alter their protein structure with age. In early stages of development smooth muscle cells surrounding blood vessels are partly reactive with some cytokeratin antibodies and with a polyclonal desmin antibody. At week 9-10 and week 25 of gestation a monoclonal antibody to desmin, however, is not reactive with blood vessel smooth muscle cells but is only reactive with smooth muscle cells surrounding bronchi. With increasing age the reactivity of cytokeratin antibodies with smooth muscle cells in blood vessels decreases, while the reactivity with the monoclonal desmin antibody increases. Our results show that during differentiation profound changes in the intermediate filament expression patterns occur in the different cell types of the developing lung.     

Expression and function of tight junctions in the crypt epithelium of human palatine tonsils.

The human palatine tonsils have surface and crypt stratified epithelium and may be initiated via the epithelium to mount immune responses to various presenting antigens. Here we investigated the expression and function of tight junctions in the epithelium of human palatine tonsils from patients with tonsillar hypertrophy or recurrent tonsillitis. Occludin, ZO-1, JAM-1, and claudin-1, -3, -4, -7, -8, and -14 mRNAs were detected in tonsillar hypertrophy. Occludin and claudin-14 were expressed in the uppermost layer of the tonsil surface epithelium, whereas ZO-1, JAM-1, and claudin-1, -4, and -7 were found throughout the epithelium. In the crypt epithelium, claudin-4 was preferentially expressed in the upper layers. In freeze-fracture replicas, short fragments of continuous tight junction strands were observed but never formed networks. In the crypt epithelium of recurrent tonsillitis, the tracer was leaked from the surface regions where occludin and claudin-4 disappeared. Occludin, ZO-1, JAM-1, and claudin-1, -3, -4, and -14, but not claudin-7, mRNAs were decreased in recurrent tonsillitis compared with those of tonsillar hypertrophy. These studies suggest unique expression of tight junctions in human palatine tonsillar epithelium, and the crypt epithelium may possess an epithelial barrier different from that of the surface epithelium.     

Morphology of complex lymphoepithelial organs of the anal canal (“anal tonsil”) in the bottlenose dolphin,Tursiops truncatus

A complex of lymphoepithelial organs, the “anal tonsils,” is a consistent structure in the anal canal of the bottlenose dolphin, Tursiops truncatus. This complex occurs as a circumferential cluster of discrete tonsil like aggregations of lymphoid tissues, together with epithelial ducts (“crypts”) and occasional mucus secretory units in the extreme lower portion of the intestinal tract. These structures are concentrated in the segment lined by stratified squamous epithelium and extend for a variable distance cephalad from the anal aperture. The tonsils appear to be most active, judged by the amount of lymphoid tissue present, in young animals. Depletion of lymphocytes and cystic enlargement of the crypts, probably representing functional as well as morphological involution, is a consistent feature of older animals. © 1995 Wiley-Liss, Inc.     

Expression of 5-lipoxygenase in specialized epithelial cells of nasopharyngeal-associated lymphoid tissue

Leukotrienes are lipid mediators that are produced primarily by certain types of leukocytes. The synthesis of the leukotriene LTB₄ is initiated by the enzyme 5-lipoxygenase and completed by LTA₄ hydrolase. Epithelial cells constitutively express LTA₄ hydrolase but normally lack 5-lipoxygenase. In this study, we report that the stratified squamous epithelial cells from inflamed or hyperplastic tissues of palatine and pharyngeal tonsils (nasopharyngeal-associated lymphoid tissue) express 5-lipoxygenase protein. The localization of 5-lipoxygenase was indicated by immunohistochemical staining and presence confirmed by immunoblot. Positive staining for 5-lipoxygenase in infiltrating leukocytes in inflamed tissues served as internal positive controls for immunohistochemical staining. Staining for 5-lipoxygenase in appendix tissue was negative for epithelial cells while positive for polymorphonuclear leukocytes, indicating that 5-lipoxygenase expression is not a general feature of epithelial cells in mucosa-associated lymphoid tissue. In tonsils, 5-lipoxygenase staining was pronounced in broad regions but reduced or absent in others, suggesting regional regulation of expression. Epithelial cells of tonsils were also positive for 5-lipoxygenase activating protein and leukotriene A₄ hydrolase, indicating a capacity to produce LTB₄. Taken together, these results suggest that the specialized epithelial cells of the mucosa-associated lymphoid tissue of human tonsils can synthesize LTB₄. This lipid mediator may serve to modulate the function of cells within the lymphoid tissue as well as promote an inflammatory response.     

Scanning, transmission and immunoelectron microscopical studies of the tonsil-like lymphoid organ of normal and horseradish-peroxidase-injected laboratory suncuses

Fine structures of normal and horseradish peroxidase (HRP)-stimulated tonsil-like lymphoid organs of the laboratory suncus (Suncus murinus) were examined by scanning, transmission and immunoelectron microscopies. The normal organs appear as a pair of small oval protrusions at the upper lateral sites of the fauces, and consist of a single lymph nodule with a germinal center and a crypt-like epithelium with prominent lymphoid cell infiltration. Postcapillary venules (PCV) and efferent lymphatics are associated within the marginal region of the nodule and separated from the neighboring pharyngeal tissues. Numerous lympho-plasma cells, interdigitating cells and reticulum cells occurred within the lymphoid parenchyma, as well as in the intraepithelial infiltrating cell populations. In the HRP-stimulated animals, the anti-HRP antibodies producing lympho-plasma cells were often seen in the parenchyma and epithelia; however, similar HRP-antibody-positive lymphocytes were rarely detected in the PCV lumina. In addition, some HRP antibody bearing interdigitating cells were also identified in the same parenchyma. These data indicate that the suncus' tonsil-like organs have a positive immune function to oral antigens, together with the suncus' systemic immune system and it is hypothetically presumed that the organ may correspond to a homologous organ of the human palatine tonsil in comparative anatomy.     

Embryogenesis of the human pharyngeal tonsil

By means of histological, histochemical, immunological and morphometric methods 78 pharyngeal tonsils of human embryos at the age of 12-40 weeks have been investigated. The character of the organ's anlage at 12-14 weeks of development as longitudinal folds on the dorsal wall of the rhinopharynx and changes in correlation of the lymphoid and epithelial tissues are presented in the process of the tonsil embryogenesis. Occupation of the organ with lymphocytes takes place on the 16th week of development. The embryos possess already two classes of T- and B-lymphocytes and their subclasses: auto-E-RFC, EAC-RFC, IgM and IgG positive cells; their kinetics is demonstrated in the process of the organ's development. A comparison on lymphocyte quantity, participating in cell-dependent immunity of the tonsil in fetuses, children and mature persons is presented.     

Age-related changes in the morphology and the distribution of IgA and IgG in the pharyngeal tonsils of yaks (Bos grunniens)

To evaluate age-related changes in the morphology as well as the expression and localization of IgA and IgG in yak pharyngeal tonsils, 20 healthy yaks were divided into four age groups [newborn (1–7 days old), juvenile (5–7 months old), adult (3–6 years old) and old (7–10 years old)]. Morphologic characteristics were observed by histological techniques. The expression and localization of IgA and IgG in pharyngeal tonsils were detected by enzyme linked immunosorbent assay (ELISA) and immunohistochemistry, respectively. The results showed that the epithelium of the pharyngeal tonsils included nonreticular epithelium with an intact basement membrane and reticular epithelium with a discontinuous basement membrane and nonepithelial cell infiltration. In newborn yaks, only primary lymphoid follicles were observed in pharyngeal tonsils. In other age groups, both primary and secondary lymphoid follicles were observed, but some of the lymphoid follicles in the old yaks were degenerated. The number of lymphoid follicles increased from the newborn to the adult group and peaked in the adult group, but the number decreased in the old group. In addition, the age-related trends of IgA and IgG protein expression were similar to those of the number of lymphoid follicles. The concentration of IgG was significantly higher than that of IgA in all age groups. Both IgA and IgG antibody secreting cells (ASCs) were distributed in the subepithelial region of the nonreticular epithelium, the reticular epithelium, the lymphoid follicles, the interfollicular areas and in between the salivary glands. The densities of IgA and IgG ASCs in pharyngeal tonsils were similar to the expression trend of both proteins in each age group. The results indicate that the morphology and amount of lymphoid follicles in yak pharyngeal tonsils vary with age. Pharyngeal tonsils produce more IgG than IgA, indicating that IgG could be significant component of mucosal immune responses in yaks.     

Computer-aided morphometric analysis of the developing concentric structure of the human fetal intestinal tube

The Image-Pro Plus 3.0 morphometric program was used to study the region-specific organization of the human fetal intestine across the radial axis of the gut at weeks 12 and 18 of gestation. The thicknesses of the epithelium, the submucosa, the muscular layers and the myenteric ganglia were measured in resin-embedded semithin sections. Statistical analysis of the collected data was performed by using the two-way ANOVA, the SNK test and the Pearson correlation. The structural changes relating to the gut morphogenesis within this developmental period were followed both light and electron microscopically. The various tissues forming the radial axis of the intestinal tube exhibited different trends concerning their individual development. The thickness of the epithelium did not change in the fetal period investigated, although the epithelial surface displayed characteristic ultrastructural changes. The thickness of the submucosal layer increased significantly, but with different dynamics along the longitudinal axis, whereas the increases in size of the muscular layers and the myenteric ganglia did not differ significantly along the longitudinal axis of the embryonic intestine. The Pearson correlation revealed a significant correlation between the development of the circular muscle layer and that of the myenteric plexus along the whole length of the intestinal tube. The epithelium, the submucosa and the longitudinal muscle layers developed independently between weeks 12 and 18 of gestation.     

Histological studies on the development of porcine tonsils after birth

Tonsils form the topographically first immune barrier of an organism against the invasion of pathogens. We used histology to study the development of tonsils of pigs after birth. At birth, the tonsils consist of diffuse lymphoid tissue without any lymphoid follicle aggregations. At the age of 7 days, lymphoid follicles appeared in the soft palate tonsil. The lymphoid layer of the nasopharyngeal tonsil, soft palate tonsil, and lingual tonsil became thicker, and lymphoid follicles in the lamina propria were clearly visible at the age of 21 days. Secondary lymphoid follicles were present in the nasopharyngeal tonsil at the age of 50 days, and in the soft palate tonsil at the age of 120 days. Dendritic cells (DCs), CD3⁺ T cells and IgA⁺ B cells in the soft palate tonsil, nasopharyngeal tonsil and lingual tonsil increased continuously, especially during the first 21 days. The results suggested that tonsils have an important role in local immune defense against invading antigens after birth and will be beneficial for understanding the mechanisms of immunity in these animals after nasal and oral vaccination.     

The epithelial origin of lymphocytes in the palatine tonsil of rabbits

Lymphopoiesis was studied by electron microscopy in the palatine tonsil of the rabbit from 18 days gestation to 5 days after birth. At 18 days tonsils formed as mounds of mesenchyma covered with epithelium. At 19 days the basal epithelial cells started to increase in number, eventually forming 'buds' which projected into the mesenchyme. Simultaneously, lymphocytes appeared nearthe epithelium or buds. There was marked resemblance between the basal epithelial cells and the lymphocytes. Budding slowed down after the 25th day, but individual basal cells continued to migrate into the mesenchyme and lymphocytes increased in number. Ultrastructure wassimilar in both types of cells, and differentfrom mesenchymal cells. At 29 days lymphocytes were found in the basal epithelial layer behind an intact basement membrane. The evidence indicated that lymphocytes were derived from epithelium.     

Tonsil-derived mesenchymal progenitor cells acquire a follicular dendritic cell phenotype under cytokine stimulation

Tonsils comprise part of the mucosal immune system and contain lymphocytes, macrophages, and follicular dendritic cells (FDCs). FDCs are located in the B cell area of the follicles of secondary lymphoid organs, such as the spleen, tonsils, or lymph nodes, and they trap and retain immune complexes on their surfaces to regulate B cell activation and maturation. Stromal cells from the palatine tonsils are often used for FDC in vitro studies, and it has been reported that human palatine tonsils may be a good source of multipotent mesenchymal cells. Therefore, we assessed whether tonsil-derived mesenchymal stromal cells could differentiate into a FDC-like phenotype. We discovered that stromal cells isolated from human tonsils not only had the potential to differentiate into various cell types of mesenchymal origin, but they also could differentiate into FDC-like cells under cytokine stimulation in vitro.     

TuJ1 (class III beta-tubulin) expression suggests dynamic redistribution of follicular dendritic cells in lymphoid tissue

Follicular dendritic cells (FDCs) play central roles in the B cell survival, proliferation, and differentiation into memory cells. Here, we show that TuJ1 (class III beta-tubulin) is expressed strongly in FDCs of human lymphoid tissue. TuJ1 has been a marker of neurons in the central and peripheral nervous systems from the early stage of neural differentiation. FDCs expressed TuJ1 protein diffusely in both light and dark zones of germinal centers in all human lymphoid tissues. In contrast, CD21 expression was relatively concentrated to the light zone, suggesting that TuJ1 was a marker for FDCs with broader spectrum than CD21. In addition to the germinal center, there were single TuJ1-expressing cells scattered in the mantle zone, blurring the border of the FDC network. In human tonsils, single scattered TuJ1-positive cells were also present in the crypt epithelium, suggesting a dynamic redistribution of FDCs among the antigen-rich epithelium, mantle zone, and germinal center. Such migration of FDCs could reflect a way of direct transport of various antigens carried on their surface to the germinal center, and a basis for the polarity of lymphoid follicles toward the epithelium in mucosa-associated lymphoid tissues. HK cells, cultured FDCs, also expressed TuJ1. The expression of TuJ1 by FDCs suggests that they may share certain biological characteristics of the neural system.     

The human thymic microenvironment. Phenotypic characterization of Hassall's bodies with the use of monoclonal antibodies

The human thymic microenvironment is important in promotion of T cell maturation, particularly during early stages of thymic ontogeny. Hassall's bodies (HB) are epithelial swirls in the human thymic medulla that are thought to be derived from endocrine medullary thymic epithelium. To study the ontogeny and function of various components of the human thymic microenvironment, we have produced four monoclonal antibodies (TE-8, TE-15, TE-16, and TE-19) that selectively reacted in thymus with HB. Antibodies TE-8 and TE-16 reacted with the cells forming the outer rim of the HB swirl. Antibody TE-19 reacted with the entire cellular portion of HB and with epithelial cells immediately surrounding HB. Granular foci in the cellular swirls of greater than 90% of HB reacted with antibody TE-15. During thymic ontogeny, the antigens defined by antibodies TE-8, TE-15, TE-16, and TE-19 were first detected in fetal thymus on HB beginning at 16 wk gestation, the age when HB morphologically appear in the thymus. Aberrant expression of the antigens corresponding to antibodies TE-8, TE-15, TE-16, and TE-19 was observed on thymic tissue from individuals with severe cellular immunodeficiency disease. In human skin, antibodies TE-8, TE-16, and TE-19 reacted with the stratum granulosum; antibody TE-15 reacted with the stratum corneum. Thus, with the use of antibodies TE-8, TE-15, TE-16, and TE-19, we have identified HB as antigenically distinct regions of endocrine thymic epithelium. Furthermore, we have shown that these anti-HB reagents also selectively react with epidermal keratinocytes in the terminal stages of keratinocyte maturation.     

Human T cell antigen expression during the early stages of fetal thymic maturation

Human thymus tissue was examined from 7 wk of gestation through birth for the expression of antigens reacting with a panel of anti-T cell monoclonal antibodies. Additionally, the reactivities of reagents against the transferrin receptor, against leukocytes, against low m. w. keratins, and against major histocompatibility complex antigens were studied on human fetal thymic tissue. Frozen tissue sections were evaluated by using indirect immunofluorescence assays. At 7 wk of gestation, no lymphoid cells were identified within the epithelial thymic rudiment; however, lymphoid cells reacting with both antibody 3A1, a pan T cell marker, and antibody T200, a pan leukocyte reagent, were identified in perithymic mesenchyme. After lymphoid colonization of the thymic rudiment at 10 wk of fetal gestation, fetal thymic tissue reacted with antibodies T1, T4, and T8. At 12 wk of gestation, antibodies T3, T6, A1G3 (anti-p80, a marker of mature thymocytes), and 35.1 (anti-E rosette receptor) all reacted with thymic tissue. Our findings indicate that T cell antigens were acquired sequentially on thymocytes at discrete stages during the first trimester of human fetal development. The 3A1 antigen was present on fetal lymphocytes before lymphoid cell colonization of thymic epithelium, suggesting that passage through the thymus was not required for the expression of the 3A1 antigen by T cell precursors. The appearance of mature T cell antigens, T3 and p80, on thymocytes by 12 wk of gestation implies that the T cell antigen repertoire may be established in the thymus during the first trimester. Thus, a critical period of T cell maturation appears to occur between 7 and 12 wk of human fetal gestation.     

Clusterin in human gut-associated lymphoid tissue, tonsils, and adenoids: localization to M cells and follicular dendritic cells

The follicle-associated epithelium (FAE) overlying the follicles of mucosa-associated lymphoid tissue is a key player in the initiation of mucosal immune responses. We recently reported strong clusterin expression in the FAE of murine Peyer’s patches. In this study, we examined the expression of clusterin in the human gut-associated lymphoid tissue (GALT) and Waldeyer’s ring. Immunohistochemistry for clusterin in human Peyer’s patches, appendix and colon lymphoid follicles revealed expression in M cells and in follicular dendritic cells (FDCs). Using cryo-immunogold electron microscopy in Peyer’s patches, we observed cytosolic immunoreactivity in M cells and labeling in the ER/Golgi biosynthetic pathway in FDCs. In palatine tonsils and adenoids, we demonstrated clusterin expression in germinal centers and in the lymphoepithelium in the crypts where M cells are localized. In conclusion, clusterin is expressed in M cells and follicular dendritic cells at inductive sites of human mucosa-associated lymphoid tissue suggesting a role for this protein in innate immune responses. Moreover, the use of clusterin as a human M cell marker could prove to be a valuable tool in future M cell research.     

Prenatal development of the palatine gland of rats

The present study aimed to elucidate the prenatal development of the rat palatine gland. Parasagittal 5 microm thick serial sections made from Wistar rats at embryonic days (E) 17 to 22 were stained with haematoxylin-eosin (HE), Alcian blue-Kernechtrot or immunohistochemistry for 5-bromo-2'-deoxyuridine (BrdU) as a marker of proliferating cells. Additionally, three-dimensional images of developing glandular parenchyma were reconstructed from serial HE sections with a personal computer. At E 17, several thickenings of the palatal epithelium had appeared which thereafter became the epithelial cords. Branching and lumenization commenced at E 20, and immature acini were observed at E 21. Three-dimensional reconstruction showed that the proximal part of the epithelial cord differentiated into the duct, and the distal part of the epithelial cord differentiated into the acinus. In immunohistochemical staining, there were many BrdU-positive cells in the epithelial cords including thickenings of the palatal epithelium, ducts, and acini. The BrdU labeling index of the cells of the epithelial cord was the highest (statistically significant) of the three in the primitive palatine gland. In conclusion, during the development of the rat palatine gland, epithelial cords with very high proliferative activity arise from the palatal epithelium, and then the proximal part of the epithelial cord differentiates into the duct, and the distal part of the epithelial cord differentiates into the acinus. Proliferation of these glandular parenchyma contributes to the growth of the developing palatine gland.