Medullary Lymphocytes Research Articles

The bursal secretory dendritic cell (BSDC) and the enigmatic chB6+ macrophage-like cell (Mal)

The bursal secretory dendritic cell (BSDC) was discovered more than 40 yr ago. It is a highly polarized, granulated cell, locating in the medulla of bursal follicle. The cytoplasmic granules either discharge or fuse together forming large, irregular-shaped, dense bodies. Formation of the dense bodies could be the first sign of BSDC transformation to macrophage-like cell (Mal) which is the result of terminal maturation of BSDC. The BSDC is non-phagocytic, unlike Mal. The discharged substance may be attached to the cell membrane (membrane-bound form) and after detaching, appears as a flocculated substance in the extracellular space of medulla. Movat pentachrome staining shows, that this substance is a glycoprotein (gp), which may be contributed to the microenvironment of the medulla. Medullary lymphocytes are floating in the gp. Precursors of the BSDC locate in the corticomedullary epithelial arches, which operate under the effect of Notch/Serrate signaling. The Notch signaling determines the fate of lymphoblast-like precursor cells and inhibits the appearance of immunoglobulin heavy chain. In the arches, the precursor cells proliferate and entering the medulla differentiate. The dense bodies pack the virus particles, which prevents the granular discharge, resulting in disappearance of extracellular gp, but gp emerges inside the virus containing Mal. In infected birds, the Mal contains either apoptotic cells or virus particles. If vaccination or infectious bursal disease virus (IBDV) infection use up the BSDC precursors, the recovery of follicle is critical.

MUFAs in High-Fat Diets Protect against Obesity-Induced Bias of Hematopoietic Cell Lineages.

The role of dietary fatty acids in the generation of bone marrow (BM) immune cells and their trafficking to extramedullary compartments in the obesity is not yet fully understood. C57BL/6J mice are randomly assigned to isocaloric high-fat diets (HFDs) formulate with dietary fats rich in saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs) or MUFAs fortified with eicosapentaenoic and docosahexaenoic acids for 20 weeks, followed by profiling of the obese metabolic phenotype and immunophenotypic features of immune cells in blood, spleen, and BM. All HFDs induce an obese phenotype, but it becomes largely less disruptive after the HFDs are enriched in MUFAs, which also induce signs of granulopoiesis and an expansion of long-term hematopoietic stem and granulocyte-macrophage progenitor cells in BM. In contrast, a HFD enriched in SFAs disturbs the fitness of medullary lymphocytes and promotes monopoiesis in favor of pro-inflammatory activated subsets. The reshaping of the fatty acid pools with MUFAs from the diet serves to manipulate the generation and trafficking of immune cells that are biased during obesity. These findings reveal a novel strategy by which dietary MUFAs may be instrumental in combating HFD-induced dysfunctional immune systems.

Infection of bursal disease virus abrogates the extracellular glycoprotein in the follicular medulla

In the medulla of bursal follicle, only the secretory dendritic cell (BSDC) is furnished with secretory machinery. The granular discharge of BSDC appears in membrane-bound and solubilized forms. Movat pentachrome staining proves that the solubilized form is a glycoprotein, which fills up the extracellular space of follicular medulla. The glycoprotein contributes to bursal microenvironment and may be attached to the surface of medullary lymphocytes. The secretory granules of BSDC may be fused, resulting in large, irregular dense bodies, which are the first sign of BSDC transformation to macrophage-like cells (Mal). To determine the effect of infectious bursal disease virus (IBDV) infection on the extracellular glycoprotein and BSDC, SPF chickens were experimentally infected with IBDV. On the surface of BSDC, the secretory substance is in high concentration, which may contribute to primary binding of IBDV to BSDC. The early distribution of IBDV infected cells is in consent with that BSDC. The IBDV infected BSDC rapidly transforms to Mal in which the glycoprotein staining appears. In the dense bodies, the packed virus particles inhibit the virus particles preventing the granular discharge, which may represent the first, early phase of virus replication cycle. The absence of extracellular glycoprotein results in alteration in the medullary microenvironment and subsequently B cell apoptosis. On the surface of medullary B cells, the solubilized secretory substance can be in much lower concentration, which results in secondary binding of IBDV to B cells. In secondary, late phase of virus replication cycle, the virus particles are not packed in electron dense substance which results in cytolytic lymphocytes and presence of virus in extracellular space. The Mal emigrates into the cortex, where induces inflammation, recruiting heterophil granulocyte and monocyte.

P2X7 blockade inhibits the growth of breast cancer in 4T1 breast cancer-bearing mice by NLRP3/caspase 1 pathway

IntroductionThe role of P2X7 in the progression of breast cancer remains unclear; hence, it is necessary to investigate whether the P2X7/NLRP3/caspase 1 signalling pathway is associated with the development of breast cancer.Material and methods4T1 breast cancer-bearing mice models were developed for P2X7 agonists BzATP and antagonists BBG. The weight of breast cancer tissue among groups was calculated and compared. The cancer tissue was observed by haematoxylin and eosin (HE) staining, and the expression of P2X7, NLRP3, and caspase 1 was examined by immunofluorescence and western blot.ResultsThe tumour weight and the medullary lymphocytes in the BzATP group were significantly higher than those of the sham and control groups, but the tumour weight and the medullary lymphocytes in the BBG group were significantly lower than those of the sham, control, and BzATP groups. The number of positive P2X7 in the BzATP group was significantly higher than that of other groups, but BBG significantly reduced the number of P2X7. The relative expression level of P2X7 in the BzATP group was significantly higher than that of other groups, but the relative expression level of P2X7 in the BBG group was significantly lower than that of other breast cancer-bearing groups.ConclusionsThe blocking of P2X7 can inhibit the growth of breast cancer in 4T1 breast cancer-bearing mice via NLRP3/caspase 1 pathway. Future studies are needed to elucidate the underlying mechanism.

Structural characterization of a novel Lactarius volemus Fr. polysaccharide and its immunity activity in BALB/c mice.

Lactarius volemus Fr. has been regarded as a great edible medicinal fungal resource in China. In this study, L. volemus Fr. polysaccharide (LVP) with an average molecular weight of 16.842 kDa was obtained by water extraction. The structure of LVP was characterized to be mannan, and the linkages in the mannan were found to comprise the Manp, (1→4)-α-Man and (1→4,6)-α-Man. Furthermore, intraperitoneal administration of LVP increased the thymus, spleen and liver indices, dose-dependently. Additionally, LVP enhanced the immune response and the phagocytic activities. Pathological evaluations showed that LVP in mice increased the proliferation of red medullary lymphocytes (60–70%). Collectively, these results indicated that LVP might be a potential resource of raw material for further investigations of functional foods.

Identification of molecular markers for pre-thrombotic state: validation in the rabbits with tibia fracture or lung cancer

Background: Currently there is no reports on identifying molecular markers for pre-thrombotic state in animal experimental settings. It’s necessary to explore the potential molecular markers for pre-thrombotic state to provide evidence for the pharmacotherapy of venous thromboembolism (VTE). Methods: A total of 36 male rabbits were randomly divided into Sham, Tibia fracture, Lung cancer, Tibia fracture and lung cancer group. Pro-thrombin time (PT), thrombin time (TT), activated partial pro-thrombin time (APTT), fibrinogen (FIB), D-dimer (D-D) and anti-thrombin III (AT-III) at baseline, 1, 7, 14 and 21 days after operation were detected. Immuno-histochemical staining of tumor tissue sections was performed to observe the expression of CD31, VEGF and vWF. Western blot and qPCR were used to detect the expression levels of ANG and VEGF gene in tumor tissues. Furthermore, we analyzed the tumor tissue with HE staining, immunochemistry, qPCR and Western blot. all the data were statistically analyzed with GraphPad Prism 6. Results: There were 0, 1, 2, 4 cases of VTE in sham, tibia fracture, lung cancer, tibia fracture and lung cancer group respectively. The level of PT, APTT, TT and AT-III were significantly decreased after operation (all P<0.05), whereas the level of FIB and D-D were significantly increased after operation (all P<0.05). The level of PT, APTT, TT and AT-III were gradually decreased in tibia fracture, lung cancer, tibia fracture and lung cancer group respectively (all P<0.05), while the level of FIB and D-D were gradually increased in tibia fracture, lung cancer, tibia fracture and lung cancer group respectively (all P<0.05). The medullary lymphocytes increased significantly in the lung cancer group, tibia fracture and lung cancer group (all P<0.05), and the number of medullary lymphocytes in tibia fracture and lung cancer group is significantly higher than that of lung cancer group (P<0.001). The expression of CD31, VEGF and vWF in Tibia fracture and lung cancer group is significantly higher than that of lung cancer group (all P<0.001). The expression ANG and VEGF in tibia fracture and lung cancer group is significantly higher than that of lung cancer group (all P<0.01). Conclusions: PT, TT, APTT, FIB, D-D and AT-III seem to be sensitive molecular markers for identifying the pre-thrombotic state. CD31, VEGF, ANG and vWF play an important role in the progression of the pre-thrombotic state.

Identification of molecular markers for pre-thrombotic state: validation in the rabbits with tibia fracture or lung cancer

BackgroundCurrently there is no reports on identifying molecular markers for pre-thrombotic state in animal experimental settings. It’s necessary to explore the potential molecular markers for pre-thrombotic state to provide evidence for the pharmacotherapy of venous thromboembolism (VTE).MethodsA total of 36 male rabbits were randomly divided into Sham, Tibia fracture, Lung cancer, Tibia fracture and lung cancer group. Pro-thrombin time (PT), thrombin time (TT), activated partial pro-thrombin time (APTT), fibrinogen (FIB), D-dimer (D-D) and anti-thrombin III (AT-III) at baseline, 1, 7, 14 and 21 days after operation were detected. Immuno-histochemical staining of tumor tissue sections was performed to observe the expression of CD31, VEGF and vWF. Western blot and qPCR were used to detect the expression levels of ANG and VEGF gene in tumor tissues. Furthermore, we analyzed the tumor tissue with HE staining, immunochemistry, qPCR and Western blot. all the data were statistically analyzed with GraphPad Prism 6.ResultsThere were 0, 1, 2, 4 cases of VTE in sham, tibia fracture, lung cancer, tibia fracture and lung cancer group respectively. The level of PT, APTT, TT and AT-III were significantly decreased after operation (all P<0.05), whereas the level of FIB and D-D were significantly increased after operation (all P<0.05). The level of PT, APTT, TT and AT-III were gradually decreased in tibia fracture, lung cancer, tibia fracture and lung cancer group respectively (all P<0.05), while the level of FIB and D-D were gradually increased in tibia fracture, lung cancer, tibia fracture and lung cancer group respectively (all P<0.05). The medullary lymphocytes increased significantly in the lung cancer group, tibia fracture and lung cancer group (all P<0.05), and the number of medullary lymphocytes in tibia fracture and lung cancer group is significantly higher than that of lung cancer group (P<0.001). The expression of CD31, VEGF and vWF in Tibia fracture and lung cancer group is significantly higher than that of lung cancer group (all P<0.001). The expression ANG and VEGF in tibia fracture and lung cancer group is significantly higher than that of lung cancer group (all P<0.01).ConclusionsPT, TT, APTT, FIB, D-D and AT-III seem to be sensitive molecular markers for identifying the pre-thrombotic state. CD31, VEGF, ANG and vWF play an important role in the progression of the pre-thrombotic state.

Abstract 4979: Multidimensional crosstalk regulates myeloid cell hyperplasia, immune escape, and tumor progression.

Abstract Myeloid-derived suppressor cells (MDSCs) encompass a heterogeneous class of cells in different maturation states that proliferate and accumulate in tumors, secondary lymphoid organs and some epithelial organs during tumor growth. Tumor secretion of growth factors and chemokines regulate myeloid cell proliferation, apoptosis, differentiation, circulation and biodistribution both locally and systemically. There is a reciprocal interaction that occurs between tumor and myeloid cells, which can facilitate tumor growth and metastasis and myeloid cell proliferation and survival via unique and tumor specific arrays of growth factors and chemokines. The tumor microenvironment, a complex, highly dynamic environment composed of host-derived MDSCs, endothelial cells, and fibroblasts; contributes to the microenvironmental crosstalk regulating host immunity and tumor progression. However, the macroenvironment is also a critical to myeloid cell expansion, tumor invasion and immune escape and tumor progression. The primary site of MDSC expansion and immune suppression is splenic extramedullary hematopoiesis, which is regulated by growth factors secreted by the distant primary tumor cells. Similarly, regulation of tumor infiltration by myeloid cells is by tumor secretion of CCL2; however, this occurs at the macroenvironmental level as CCL2/CCR2 blockade inhibits medullary myeloid cell mobilization and recruitment from secondary lymphoid organs and not at the tumor. Further, regulatory crosstalk is bidirectional with tumor-secreted factors differentially upregulating myeloid and lymphoid cell growth factors and enzymes (G-CSF, CXCL1, CCL2, arginase) by medullary myeloid cells and splenic lymphocytes. In tumor bearing, mice the tumor-secreted growth factors support hematopoietic stem/progenitor cell proliferation, limit their apoptosis and inhibit T-cell function. Conversely, leukocyte-secreted cytokines limit immune and hematopoietic growth factor transcript levels by tumor cells (G-CSF, IL-23, CXCL1 and NOS-2) with associated effects on tumor malignancy and leukocyte proliferation and differentiation. In summary, tumors form both local and systemic, bidirectional, regulatory loop(s) between metastatic tumor cells and MDSCs that regulates their proliferation and differentiation supporting tumor metastasis and systemic and regional T-cell suppression. Citation Format: Ibrahim H. Younos, Alicia J. Dafferner, Holly Britton, James E. Talmadge. Multidimensional crosstalk regulates myeloid cell hyperplasia, immune escape, and tumor progression. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4979. doi:10.1158/1538-7445.AM2013-4979

Expression of bcl-2 in fetal thymus, thymomas and thymic carcinomas. Association with p53 expression and review of the literature.

Bcl-2 is a proto-oncogene inhibiting apoptosis, and p53 is a tumor supressor gene which induces apoptosis. Both seem to take part in tumorigenesis. An inverse relationship between the two genes has been reported in some neoplasms, although the exact mechanism is not fully understood. We have analyzed the expression of bcl-2 and p53 in 18 fetal thymuses and 18 clinically benign and malignant thymomas: bcl-2 was expressed by most medullary lymphocytes and epithelial cells of the normal thymus; p53 was not expressed at all. Bcl-2 and p53 were co-expressed in the majority of the thymomas and the staining reaction was stronger in the clinically malignant ones. It is concluded that although co-expression of bcl-2 and p53 is of doubtful prognostic relevance, the staining pattern of bcl-2 supports the histogenetic classification system of Müller-Hermelink.

Three-dimensional ultrastructure of the perivascular space in the rat thymus.

The overall architecture and structure of the perivascular space in the rat thymus were studied by light microscopy using silver-impregnated sections and sections stained immunohistochemically with anti-cytokeratin antibody, and by transmission and scanning electron microscopy (TEM and SEM). In silver-impregnated sections, the perivascular space was delimited by a thin sheath of delicate argyrophilic fibers from the thymic parenchyma in the cortico-medullary region and medulla. This space was continuous with the septal connective tissue, indicating that this was the connective tissue compartment rather than with the epithelial compartment of the parenchyma. In the medulla, the perivascular space widened at places, where the argyrophilic sheath was often discontinuous and the boundary between the perivascular space and parenchyma was indistinct. Lymphatics were located in the perivascular space of the corticomedullary region and sometimes in the wide perivascular space of the medulla. The presence of a thymic epithelial sheath surrounding the perivascular space was confirmed by light microscopy of anti-cytokeratin antibody immunostained sections and by TEM. SEM observations revealed three-dimensionally that the epithelial sheath lined by collagen fibrillar (i.e., argyrophilic) layer form a rather continuous tubular structure in the cortico-medullary region, while it often interrupted in the medulla. These findings indicated that the perivascular space (i.e., the connective tissue compartment) is extensively open to the parenchyma (i.e., the epithelial compartment) in some portions of the medulla, where medullary lymphocytes are probably freely exposed to blood borne substances similar to the peripheral lymphoid tissues.

Spectrin localizations in the chicken bursa of Fabricius at different stages of development

Before and after hatching, light microscopic and ultrastructural observations of spectrin were performed immunohistochemically in the chicken bursa of Fabricius. Before hatching, the frequency of spectrin-positive cells was very low. Among the spectrin-positive cells spectrin was mostly detected in patchy or diffuse form in the cytoplasm and rarely seen at surface membranes. Although cortical lymphocytes were spectrin-negative, numerous medullary lymphocytes were spectrin-positive after hatching. In the medullary spectrin-positive cells, staining intensity was uniform. Spectrins showed ultrastructural heterogeneity after hatching. Although a new type of spectrin localization associated with surface membranes was observed, this type of spectrin localization was not prominent. The increased number of spectrin-positive cells, uniform staining intensity and the localization of spectrin associated with surface membranes seem to coincide with B cell differentiation.

A microscopic investigation of the lymphoid organs of the beluga, Delphinapterus leucas.

Lymphoid organs from belugas, Delphinapterus leucas, ranging in age from less than one to 16 years, were harvested during a sanctioned hunt to investigate morphology. The spleen is divisible into red and white pulp and a stroma consisting of a reticular network, a collagenous capsule, and trabeculae containing smooth muscle bundles. White pulp areas appear to be devoid of follicles and consist mainly of periarteriolar lymphatic sheaths (PALS), that are larger in younger than in older belugas. Definitive marginal zones between red and white pulp are difficult to discern in older belugas. Lymph nodes are similar to those of other mammals; they possess a follicular cortex surrounding a vascular medulla composed of lymphatic cords and sinuses. Smooth muscle is abundant in the medullary region, usually in close proximity to sinuses. The expansive nodular mass at the root of the mesentery, often referred to as the "pseudopancreas," is similar to lymph nodes in microscopic architecture. Pharyngeal tonsils and gut-associated lymphoid tissue (GALT) are found along the digestive tract and display an "active" morphology. Tonsils are comprised of lobules of follicles separated by vascular connective tissue. Epithelial-lined crypts communicate with the pharyngeal lumen. GALT consists of diffuse and follicular lymphocytes within the intestinal mucosa and submucosa. The thymus is well developed in the younger belugas, with lobules divisible into densely packed cortical zones of thymocytes and more loosely arranged medullary lymphocytes. Hassall's corpuscles are occasionally visible within the medulla. Cetaceans diverged evolutionarily from other mammals over 55 million years ago. This study investigates changes in lymphoid organ morphology in a species that now inhabits a unique ecological niche. This study also lays the groundwork for functional investigation of the beluga immune system, particularly as it relates to differences between healthy and stranded animals.

Changes in the thymus and spleen of the turtle Mauremys caspica after testosterone injection: A morphometric study

To confirm a possible role of sex hormones in governing the seasonal variations affecting the reptilian lymphoid organs, a morphometric analysis was carried out on the thymus and spleen of turtles, Mauremys caspica, intraperitoneally injected with a single dose of testosterone propionate (TP) at the third week of June when physiological levels of testosterone are low. At 4 and 6 weeks, control turtles show an apparent lymphocyte mobilization both from thymus and spleen with a decrease in the percentage of thymic cortex, numbers of cortical lymphocytes, and mitotic index, but increased numbers of medullary lymphocytes. In the thymic cortex of treated turtles, there is a decrease in the same parameters but they occur in the first 2 weeks, whereas the medullary lymphocytes also undergo reduction at 4 and 6 weeks. In addition, the number of reticuloepithelial cells per area unit decreases at 2 weeks in the thymic cortex of treated turtles. These results are discussed from the point of view of a biphasic effect of testosterone on turtle lymphoid organs: In the first weeks, the changes observed could be attributed to the high levels of testosterone; after 4 and 6 weeks, variations are dependent both on long-term effects of testosterone and on those induced by the high values of corticosterone occurring in summer.

Extracellular matrix of lymphoid tissues in the chick.

We describe the immunohistochemical distribution of components of the extracellular matrix of the chick lymphoid system. In the thymus, basement membranes of epithelial cells bordering the lobules were intensely stained by laminin antibodies; fibronectin antibodies labeled the capsule and the septal matrix, and similar reactivity was seen with tropoelastin and gp 115 antibodies. No positivity was detected with any of the antibodies within the cortical parenchymal cells. Laminin was not detected in the medullary parenchyma, whereas fibronectin was present as coarse fibers. Tropoelastin and gp 115 appeared as a finer and more diffuse meshwork. In the bursa, laminin antibodies outlined the epithelial cells separating the cortex from the medulla. Fibronectin, tropoelastin, and gp 115 antibody stained the interfollicular septa and the cortical matrix, although to a different extent. Laminin was also detected in association with the interfollicular epithelium (IFE) basement membrane, whereas no staining was found underneath the follicle-associated epithelium (FAE). FAE cells not only lack a proper basement membrane but are also not separated from medullary lymphocytes by any of the other extracellular matrix components were investigated. Consequently, medullary lymphocytes are not sequestered, and can come easily into contact with antigens present in the intestinal lumen. All four antibodies stained the spleen capsule and spleen blood vessels, tropoelastin and gp 115 antibodies giving the strongest reactivity. A fine trabecular staining pattern was detected with gp 115 antibodies in the white pulp.

Immunochemistry of highly branched N-glycans. Terminal N-acetyl-D-glucosamine (GlcNAc) cluster antigens contain epitopes composed of terminal GlcNAc residues linked to mannose

We have previously demonstrated by the immunoperoxidase method the presence of a chicken heterophile antigenic determinant (CHAD-1) in medullary lymphocytes of the bursa of Fabricius and thymus as well as in some nonlymphoid cells. It has been found that the anti-CHAD-1 antibody could be neutralized by absorption with several glycoproteins or glycopeptides containing highly branched, asparagine-linked oligosaccharides terminating in N-acetylglucosamine residues. In the present study, fetuin, desialo-fetuin, and a series of 27 highly purified oligosaccharides with well-defined structures were used to investigate the chemical composition and fine structure of the CHAD-1 epitope. It was shown that anti-CHAD-1 antibody binds to oligosaccharides with at least three terminal N-acetyl glucosamine residues at the nonreducing end. These residues may be linked beta 1-2, beta 1-4, or beta 1-6 to one, two, or three different mannose residues. The antibody combining site accommodates at least four carbohydrate residues. Oligosaccharides containing five or six terminal N-acetylglucosamine residues at the nonreducing end demonstrated the highest immunoreactivity with the anti-CHAD-1 antibody. Substitution of terminal N-acetylglucosamine residues with galactose, or with galactose and sialic acid, masks CHAD-1. On the basis of this work, epitopes that react with the anti-CHAD-1 antibody will be renamed terminal N-acetylglucosamine cluster antigens (TGCA). Anti-TGCA antibody has potential use in the monitoring of biosynthetic processing of asparagine-linked oligosaccharides and in studies of their cellular distribution and functions.

Identification of terminal N-acetylglucosamine residues of highly branched asparagine-linked oligosaccharides as immunoreactive domains of a chicken heterophile antigenic determinant

Chicken heterophile antigenic determinant (CHAD-1) has been previously found in medullary lymphocytes of the bursa and thymus as well as in some non-lymphoid cells by the immunoperoxidase method, using rabbit antiserum to a complete Freund's adjuvant (CFA) as the first antibody. In this work we demonstrated that absorption of anti-CFA serum with highly purified preparations of hen egg white glycoproteins (ovomucoid, ovoinhibitor, ovalbumin) or chicken orosomucoid completely blocked immunoperoxidase staining for CHAD-1. Treatment of these glycoproteins with β- N-acetylglucosaminidase suppressed their capacity to inhibit this staining. Absorption of anti-CFA serum with asparagine-linked glycopeptides which have the mannose α1,3 arm disubstituted by GlcNAc residues and which have another GlcNAc residue linked β 1,4 to the β-linked mannose of the core also inhibited staining for CHAD-1. These data indicated that highly branched asparagine-linked oligosaccharides with terminal GlcNAc residues β-linked to mannose represent immunoreactive domains of CHAD-1.

Papovavirus Infection in Hand-Fed Parrots: Virus Isolation and Pathology

Papovavirus infection was diagnosed in 44 parrots of at least 18 species exclusive of the budgerigar (Melopsittacus undulatus). The birds were 14 days to 4 months old and had been removed from parental care and hand-fed as nestlings. The birds had been unexpectedly found dead after having evidenced no premonitory signs of illness, or they died following a short (12-to-48-hour) period of lassitude and anorexia. In most cases, necropsies revealed pallor, multiple hemorrhages, splenomegaly, and hepatomegaly with multifocal necrosis. Histological lesions included multifocal to diffuse hepatic necrosis that spared the periportal hepatocytes, karyomegaly of splenic reticuloendothelial cells and cells in other tissues, membranous glomerulopathy, and necrosis of bursal medullary lymphocytes. Papovaviruses were isolated from two cases, and papovavirus infection was confirmed in 27 of the birds by the fluorescent-antibody test using a conjugate against a papovavirus isolated from a budgerigar.

Enzymatic and morphological response of the thymus to drugs in normal and zinc-deficient pregnant rats and their fetuses.

In the thymus of normally fed pregnant rats the plasma membrane enzymes dipeptidyl peptidase IV (DPP IV) and alkaline phosphatase (alP) were found in cortical and medullary lymphocytes (thymocytes). Plasma membrane aminopeptidase A (APA) and adenosine monophosphate hydrolysing phosphatase (AMPP) were present in cortical reticular cells. In medullary reticular cells, aminopeptidase M (APM), gamma-glutamyl transferase (GGT), adenosine triphosphate (ATPP) and thiamine pyrophosphate (TPPP) cleaving phosphatases were detected. Medullary reticular cells did not contain APA. Lysosomal DPP I and II, acid phosphatase, acid beta-D-galactosidase, beta-D-N-acetyl-glucosaminidase, beta-D-glucuronidase and non-specific esterases occurred especially in macrophages at the corticomedullary junction. The 21-day-old fetal thymus showed a similar reaction pattern as the maternal organ except for APA which was absent before birth. After treatment of the pregnant rats with valproic acid (VPA), salicylic acid (SA), streptozotocin (ST) and retinoic acid (RA) APA showed an increase in activity in the thymic cortex. In addition, ST and RA induced AMPP, ATPP and TPPP activity in cortical reticular cells up to the same pattern as in medullary reticular cells. After ethanol (ET) administration severe damages occurred. The thymic cortex was free of DPP IV-positive lymphocytes; the medullary reticular cells showed reduced or no GGT and occasionally an increased APM activity. Dexamethasone (DEXA) given to normal or zinc-deficient rats produced the most severe lesions; thymocytes with DPP IV activity were completely absent in the cortex and medulla. In Zn-deficient pregnant rats similar alterations were observed as after ET.(ABSTRACT TRUNCATED AT 250 WORDS)

A scanning electron-microscopic study of the rat thymus with special reference to cell types and migration of lymphocytes into the general circulation.

The three-dimensional structure of the rat thymus was studied by combined scanning- and transmission electron microscopy. The thymus consists mainly of four types of cells: epithelial cells, lymphocytes, macrophages, and interdigitating cells (IDCs). The epithelial cells form a meshwork in the thymus parenchyma. Cortical epithelial cells are stellate in shape, while the medullary cells comprise two types: stellate and large vacuolated elements. A continuous single layer of epithelial cells separates the parenchyma from connective tissue formations of the capsule, septa and vessels. Surrounding the blood vessels, this epithelial sheath is continuous in the cortex, while it is partly interrupted in the medulla, suggesting that the blood-thymus barrier might function more completely in the cortex. Cortical lymphocytes are round and vary in size, whereas medullary lymphocytes are mainly small, although they vary considerably in surface morphology. Two types of large wandering cells, macrophages and IDCs, could be distinguished, as well as intermediate forms. IDCs sometimes embraced or contacted lymphocytes, suggesting their role in the differentiation of the latter cells. Perivascular channels were present around venules and some arterioles in the cortico-medullary region and in the medulla. A few lymphatic vessels were present in extended perivascular spaces. The present study suggests the possible existence of two routes of passage of lymphocytes into the general circulation. One is via the lymphatics, while the other is through the postcapillary venules into the blood circulation. Our SEM images give evidence that lymphocytes use an intracellular route, i.e., the endothelium of venules.

Expression of major histocompatibility complex antigens in the thymuses of chimeric mice.

Thymuses of various types of bone-marrow-chimeric mice have been examined by tissue section immunologic staining for the presence and distribution of major histocompatibility complex (MHC) antigens. Cortical and medullary thymic epithelial cells continue to express thymus genotype I-A and H-2K/D antigens for at least 6 months posttransplantation. The appearance of bone-marrow-type MHC antigens is limited to low levels of H-2K/D on cortical and medullary lymphocytes, and to dendritic cells in the medulla; the medullary dendritic cells express high levels of donor-type I-A antigens as soon as 3 weeks posttransplantation. The observed patterns support the concept that I-A antigens are synthesized by thymic epithelial cells but are acquired by thymocytes. The findings are of relevance to the understanding of the role of the thymus in the generation of MHC restriction.