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PubMed1983

Studies of intestinal lymphoid tissue. VII. The secondary nature of lymphoid cell "activation" in the jejunal lesion of tropical sprue.

Morphometric techniques were used in the evaluation of lymphocyte morphology and activity in tropical sprue. jejunal biopsies from control subjects (8), patients with epidemic disease (7), patients with endemic disease (11), and subjects who had recovered from sprue (4) were analyzed blindly. In patients with sprue, lymphocytes were increased significantly within crypt (but not surface) epithelium. Immunoblasts (greater than 6 mu in diameter) were increased by 5% over control subjects. Group means for lymphocytic mitotic indexes were also significantly raised, while flux ratios only differed significantly between endemic sprue patients and control subjects. The lymphocytic infiltration was distributed focally in the upper crypt and crypt-villus interzones. Analysis of epidemic cases (presenting within 4-28 days) revealed detectable changes in lymphocyte behavior only after 3 weeks' illness, whereas mucosal lesions and malabsorption were already established during the first week. These data indicate that lymphocyte activation, suggestive of a local cell-mediated immune reaction, does occur in tropical sprue but is secondary to damage already inflicted on enterocytes and their function.

Adult↗
PubMed1987

Phenotypic expression of cells of stationary elements in human lymphoid tissues. A histochemical and immunohistochemical study.

The stationary elements of lymphoid tissues are composed of four types of cells: histiocytes, interdigitating reticulum cells, follicular dendritic cells, and fibroblastic reticulum cells. The phenotypes of these cells were determined with a large panel of monocyte/histiocyte, C3 receptor monoclonal antibodies, and others. Based on the monocyte-marker expression, histiocytes can be separated into two groups: (1) free histiocytes (monocyte-marker positive) and (2) fixed histiocytes (monocyte-marker negative). The former are characterized by the expression of monocyte markers, such as OK M1, Co Mo2, BRL Mol/Mo2, and Leu M3, whereas the latter are not. Interdigitating reticulum cells are localized in the T-cell zone. These cells are characterized by the expression of 1E9, 2H9, and Leu M1. Interdigitating reticulum cells and fixed histiocytes are similar in terms of marker expression and enzyme histochemistry. However, in interdigitating reticulum cells, the Leu M1 antigen is localized on the membrane, in contrast to histiocytes, in which it has a Golgi distribution. Follicular dendritic cells are present in germinal centers and mantle zones. These cells express complement (C3) receptors and several monocyte markers (including OK M1 and Co Mo2). Follicular dendritic cells are capable of trapping antigens onto their membranes. This unique property makes us reluctant to conclude that follicular dendritic cells are related to monocytes. Fibroblastic reticulum cells express BA-1 and alkaline phosphatase, and they form a dendritic network, especially in the T-cell zone. The results of this study demonstrate that immunoperoxidase staining with monoclonal antibodies can reveal the distribution of histiocytes and dendritic/reticulum cells in lymphoid tissues.

Antibodies, Monoclonal↗
PubMed1980

Selective labelling of lymphoid tissues by extracorporeal perfusion.

A method for selective labelling of lymphoid tissues by means of an extracorporeal perfusion system is described. The applicability of this technique was tested by local labelling of a part of the small intestine with its mesenteric lymph nodes, spleen and bone marrow in normal young pits. Tritiated thymidine was added to the perfusate and the selectivity of the labelling procedure tested by scintillation counting of serum samples, of specimens of lymphoid tissues and by autoradiography. There was only negligible spillover of the isotope and the perfused organs were well preserved.

Animals↗
PubMed1981

Immunohistological analysis of human lymphoid tissue by double immunoenzymatic labelling.

The increasing number of antigens detectable in human lymphoid tissue (particularly since the advent of monoclonal antibodies) makes it necessary to have techniques available for studying the relative distribution patterns of pairs of antigens in tissue sections. Double immunoenzymatic labelling (using peroxidase and alkaline phosphatase) offers a number of advantages over double immunofluorescence, including the fact that the two antigens can be visualised simultaneously (rather than sequentially) and that the labels are permanent. In studying paraffin-embedded human lymphoid tissue an important application of the double immunoenzymatic technique lies in distinguishing Ig-positive cells containing exogenous Ig (which stain for only a single light chain class). In addition double staining of paraffin sections for IgG and IgM has been used to show that "switch" cells containing both these classes of heavy chain are rare in reactive lymphoid tissue. The potential scope of the double immunoenzymatic technique has been extended by showing that the procedure is applicable to cryostat sections (in which antigenic reactivity is better preserved than in paraffin sections) and by adapting it for use with monoclonal antibodies (by preparing "monoclonal PAP" complexes).

Antigens↗
PubMed1989

Investigation of bovine gut associated lymphoid tissue (GALT) using monoclonal antibodies against bovine lymphocytes.

Gut associated lymphoid tissue of the small and large intestine of calves and cows has been compared morphologically and quantitatively using monoclonal antibodies to bovine lymphocytes. B cells were significantly decreased in the ileum of the cow compared to the calf. Significantly increased numbers of T cells were present in cell suspensions of all lymphoid areas of the cow compared to the calf. T lymphocyte subsets were quantified into cryostat sections of lymphoid tissues expressing BoT4, and BoT8 antigens demonstrated increased numbers in follicular and dome areas of the discrete Peyer's patches of the small and large intestine of the cow. BoT4+, BoT8+, and the non-BoT4/BoT8+ T cell subsets were increased in the mucosa of the cow as compared to the calf. Similarities in structure and lymphocyte composition of the discrete Peyer's patches of the small intestine, cecum and colon and isolated single follicles in the large intestine suggest similar functional properties.

Analysis of Variance↗
PubMed1994

Lymphoid tissues induce NGF-dependent and NGF-independent neurite outgrowth from rat superior cervical ganglia explants in culture.

Induction of neurite outgrowth from superior cervical ganglia (SCG) by rat lymphoid tissues was studied using a tissue culture model. Neonatal rat SCG were cultured with 6-12-week-old rat thymus, spleen, or mesenteric lymph node (MLN) explants in a Matrigel layer, in defined culture medium without exogenous nerve growth factor (NGF). SCG were also co-cultured with neonatal rat heart (as positive control) or spinal cord (SC; as negative control). To determine whether inflammation affects the ability of lymphoid tissues to induce neurite outgrowth, we also examined MLN at various times after infecting rats with Nip-postrongylus brasiliensis (Nb-MLN). In one series of experiments, a single lymphoid tissue explant was surrounded by four SCG at a distance of 1 mm. The extent of neurite outgrowth was determined by counting the number of neurites 0.5 mm away from each ganglion at several time points. Adult thymus and, to a lesser extent, spleen had strong stimulatory effects on neurite outgrowth from SCG after 12 hr or more in culture. For thymus tissue, this was similar to the positive control heart explants. MLN from normal rats had minimal effect on neurite outgrowth; however, Nb-MLN showed a time-dependent enhancement of the neurite outgrowth, maximal at 3 weeks after infection. The relative efficacy of neurite outgrowth induction (heart > or = thymus > or = Nb-MLN > or spleen > or = MLN > or = SC) was confirmed in a second series of experiments where one SCG was surrounded by three different tissue explants. We then examined the role of 2.5S NGF, a well-known trophic factor for sympathetic nerves, in the lymphoid tissue-induced neurite outgrowth. Anti-NGF treatment of co-cultures of SCG and heart almost completely blocked the neurite outgrowth. Anti-NGF also significantly inhibited thymus- and spleen-induced neurite outgrowth, but not as effectively as heart-induced neuritogenesis (93, 80, and 77% inhibition at 24 hr; 86, 70, and 68% inhibition at 48 hr for heart, thymus, and spleen, respectively). On the other hand, anti-NGF inhibited only 8% of neurite outgrowth induced by 3-week post-infection Nb-MLN at 24 hr, and 41% at 48 hr. These data show that several adult rat lymphoid tissues exert neurotrophic/tropic effects. The predominant growth factor in thymus and spleen is NGF, while Nb-MLN produces factor(s) which is (are) immunologically distinguishable from NGF.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2002

The development of primary and secondary lymphoid tissues in the nurse shark Ginglymostoma cirratum: B-cell zones precede dendritic cell immigration and T-cell zone formation during ontogeny of the spleen.

Secondary lymphoid tissue and immunoglobulin (Ig) production in mammals is not fully developed at birth, requiring time postnatally to attain all features required for adaptive immune responses. The immune system of newborn sharks - the oldest vertebrate group having adaptive immunity - also displays immature characteristics such as low serum IgM concentration and high levels of IgM1gj, an innate-like Ig. Primary and secondary lymphoid tissues in sharks and other cartilaginous fish were identified previously, but their cellular organization was not examined in detail. In this study of nurse shark lymphoid tissue, we demonstrate that the adult spleen contains well-defined, highly vascularized white pulp (WP) areas, composed of a central T-cell zone containing a major histocompatibility complex (MHC) class II+ dendritic cell (DC) network and a small number of Ig+ secretory cells, surrounded by smaller zones of surface Ig+ (sIg+) B cells. In neonates, splenic WPs are exclusively B-cell zones containing sIgM+-MHC class IIlow B cells; thus compartmentalized areas with T cells and DCs, as well as surface Ig novel antigen receptor (sIgNAR)-expressing B cells are absent at birth. Not until the pups are 5 months old do these WP areas become adult-like; concomitantly, sIgNAR+ B cells are readily detectable, indicating that this Ig class requires a 'mature immune-responsive environment'. The epigonal organ is the major site of neonatal B lymphopoiesis, based on the presence of developing B cells and recombination-activating gene 1 (RAG1)/terminal deoxynucleotidyl transferase (TdT) expression, indicative of antigen receptor rearrangement; such expression persists into adult life, whereas the spleen has negligible lymphopoietic activity. In adults but not neonates, many secretory B cells reside in the epigonal organ, suggesting, like in mammals, that B cells home to this primary lymphoid tissue after activation in other areas of the body.

Animals↗
PubMed2002

Segregation of R5 and X4 HIV-1 variants to memory T cell subsets differentially expressing CD62L in ex vivo infected human lymphoid tissue.

OBJECTIVE: The mechanisms of HIV-triggered immunodeficiency were examined by determining the segregation of R5 and X4 HIV-1 variants into memory T cell subsets expressing differentially a homing receptor, CD62L-selectin, in human lymphoid tissue. METHODS: Subpopulations of CD3 and intracellular p24 gag-positive cells in human lymphoid tissue infected ex vivo with X4 HIV-1 variant NL4-3 and R5 HIV-1 variant AD8 were analysed for expression of the T cell memory markers CD45RO and CD45RA, the T cell homing receptor for lymphoid tissue CD62L, and the HIV-1 coreceptors CCR5 and CXCR4. RESULTS: Memory CD4 T cells were the predominant targets for productive infection of lymphoid tissue ex vivo with both R5 and X4 HIV-1. R5 HIV-1 predominantly infected CD62L-negative memory T cells, which selectively express CCR5. In contrast, X4 HIV-1 variants predominantly infected CD62L+ memory T cells, although CXCR4 coreceptor was equally expressed by memory T cells of both CD62L-positive and CD62L-negative subsets. A high proportion of X4 HIV-1, but not of R5 HIV-1, productively infected T cells, displayed a CD45RA+CD45RO+ phenotype. CONCLUSION: The selective expression of the CCR5 coreceptor by CD62L-negative terminally differentiated memory T cells correlates with the preferential productive infection of these cells with the R5 HIV-1 variant. The predominance of X4 HIV-1 variants in less-differentiated memory T cells may be related to their recent activation state, as suggested by the coexpression of both CD45RA and CD45RO molecules on their surface. Differential homing of CD62L-positive and CD62L-negative cells suggests different routes of dissemination of X4 and R5 viruses.

CD4-Positive T-Lymphocytes↗
PubMed1991

Follicle associated epithelium of the gut associated lymphoid tissue of cattle.

The morphology of the gut-associated lymphoid tissue of the small and large intestine in three gnotobiotic calves was examined by scanning and transmission electron microscopy, and the distribution of specialized membranous cells present in the follicle associated epithelium was defined. Isolated follicles remaining in the ileum of a cow after involution of the continuous Peyer's patch were examined by scanning electron microscopy. The presence of membrane-bound particles, reported to be exclusively associated with the continuous Peyer's patch, was investigated in other gut-associated tissue of the small and large intestine of the calf. The presence of two types of follicle associated epithelium in the small intestine of the calf was confirmed, and the follicle associated epithelium of the large intestine proved to be a homogeneous population of specialized membranous cells, similar to that of the continuous Peyer's patch of the small intestine. In the discrete Peyer's patches, some specialized membranous cells were completely hidden by adjacent enterocytes and could only be identified by cytoplasmic extensions into the intestinal lumen. In the proximal part of the continuous Peyer's patch, a transitional zone was detected where the follicle associated epithelium of some doomed villi was composed of a homogeneous population of specialized membranous cells, while the epithelium covering other doomed villi consisted of a mixture of absorptive and specialized membranous cells, usually only found in the discrete Peyer's patches. Membrane-bound particles were observed associated with gut-associated lymphoid tissue in the small and large intestine.

Animals↗
PubMed1991

Microvascular architecture of rat nasal associated lymphoid tissue.

The blood vascular architecture of the rat nasal associated lymphoid tissue (NALT) was studied by scanning electron microscopy of corrosion casts. To examine the correlation of the vasculature with the distribution of lymphocyte subsets, the NALT was also studied by light microscopy of immuno-stained samples. The NALT was supplied by a branch of the inferior nasal artery which arose from the sphenopalatine artery. This branch reached the bottom of the NALT and ramified arterioles to the follicles and the parafollicular regions. These arterioles ascended toward the subepithelial region, giving off capillaries en route to form a coarse plexus within the follicles and the parafollicular regions. The arterioles reached the subepithelial region and formed a subepithelial capillary network consisting of a single layer of flat meshwork. The follicular, parafollicular and subepithelial capillaries anastomosed one another. The capillaries in each region were gathered into collecting venules, which in turn drained into high endothelial venules (HEVs) in the parafollicular region. The HEVs ran through the parafollicular regions around the follicular perimeters, and flowed into ordinary veins to leave the NALT. Lymphocytes labeled with an anti-T cell antibody were mainly distributed in the parafollicular regions, where HEVs were situated. B cells were mostly observed in the follicular and dome areas. The microvascular structure and its correlation with lymphocyte subset domains in the NALT were essentially similar to those in other mucosa associated lymphoid tissues (MALTs) such as tonsils and Peyer's patches.

Animals↗
PubMed2000

The roles of histology and immunohistology in the investigation of marsupial disease and normal lymphoid tissue.

This review acquaints scientists with current information related to the application of histology and immunohistology to the studies of normal lymphoid tissues and specific diseases in marsupials. Histological examination of tissue is a necessary prerequisite for immunohistological examination because it establishes tissue structure and detects specific areas of disease which allow the selection of smaller areas for immunohistological examination. Information is provided on the basic techniques of histology. Immunohistology (immunohistochemistry) refers to the identification of antigenic determinants of specific substances (proteins) by the application of antibodies to histological sections. Information is provided on a technique for enzyme based, avidin-biotin enhanced immunohistology, and on antibodies that can be used to mark disease agents or marsupial tissues and cells. A summary is provided of the available information on studies of the histology and immunohistology of normal marsupial lymphoid tissue (thymus, spleen, lymph nodes and mucosa associated lymphoid tissue), and of selected marsupial diseases such as chlamydiosis and lymphosarcoma in koalas.

Animals↗
PubMed1992

Immunohistochemical demonstration of interleukin-1 receptor antagonist protein and interleukin-1 in human lymphoid tissue and granulomas.

Human interleukin 1 receptor antagonist protein (IRAP) is a specific antagonist of interleukin 1 (IL-1) action in both in vitro and in vivo experimental models. Presently, the significance of this protein in human pathophysiology is unknown. In the present study, monoclonal antibodies against IRAP were prepared and used to demonstrate IRAP expression in human tissues, immunohistochemically. Specifically, this study focused on lymphoid tissues and granulomatous inflammatory reactions since IL-1 is believed to play roles in lymphocyte development and inflammation. In addition, these tissues were also stained for IL-1 beta to compare the expression of agonist and antagonist. These findings indicate that IRAP expression is largely limited to macrophages and their derivatives. Strong IRAP expression was observed in germinal center macrophages of lymph nodes, spleen, and tonsil. In contrast, IL-1 was marginally expressed in these organs. Granulomas associated with active M. tuberculosis infection, sarcoidosis and foreign bodies all contained strongly IRAP positive cells, which included macrophages, epithelioid cells and multinucleate giant cells. Unlike reactive lymphoid tissue, tuberculous and sarcoid granulomas also contained IL-1 positive cells which included macrophages and their derivatives, as well as some stromal cells. Foreign body lesions showed minimal IL-1 expression. Interestingly, granulomas in patients with acquired immunodeficiency disease (AIDS) associated with M. avium-intracellulare contained IRAP positive cells but were negative for IL-1 expression. Taken together, these findings suggest that IRAP takes part in both physiologic and pathologic reactions. Moreover, they provide a basis to design future studies to determine the precise contribution of IRAP to these reactions.

Granuloma↗
PubMed1985

Applicability of imprints to immuno-ultrastructural studies of lymphoid tissues.

In order to evaluate the applicability of imprints to immuno-ultrastructural studies of lymphoid tissues, we compared distribution pattern and morphology of B cells, T cells, T-cell subsets, and follicular dendritic reticulum cells (DRC) at the light and ultrastructural level in imprints and sections of tonsils and lymph nodes. The surface antigenic profile of lymphoid cells was revealed with monoclonal antibodies in an avidin-biotin-peroxidase complex (ABC) method. Distribution of lymphoid cells in coherent areas of imprints recapitulated their disposition in sections of respective lymphoid tissues. Preservation of microanatomical relationships and ultrastructure of lymphoid cells in imprints allowed evaluation of associations and fine structural detail of lymphoid cells. Morphologic configurations of B cells in imprints, confined to round aggregates, were similar to fine structural morphology of B cells in mantle zones (MZ) and germinal centers (GC). Processes of DRCs in imprints formed conformations resembling their meshwork within follicles and mantled lymphoid cells. In imprints and sections, lymphocytes of cytotoxic/suppressor phenotype had a large amount of cytoplasm with many organelles. In contrast, cells of helper/inducer phenotype displayed a high nucleocytoplasmic (N/C) ratio and small numbers of organelles. Thus, imprints represent an easy, fast, and reliable method that lends itself to immunoultrastructural studies of lymphoid tissues.

Antibodies, Monoclonal↗
PubMed1999

Lymphocyte subsets in neonatal and juvenile cats: comparison of blood and lymphoid tissues.

OBJECTIVE: To compare lymphocyte subpopulations in the blood and lymphoid tissues of normal kittens between 1 and 90 days of age. METHODS: Lymphocyte subsets within the blood, thymus, and lymph node of 24 normal kittens were quantified by use of two-color fluorescence flow cytometry and were compared at 1, 23, 46, or 90 days after birth. RESULTS: Blood B and T lymphocytes increased over the 90-day postnatal period. The CD4+ and CD8+ sub-populations of T lymphocytes increased. However, CD8+ lymphocytes increased more than did CD4+ lymphocytes, resulting in reduced CD4-to-CD8 ratio. By 23 days of age, similar but more abrupt changes in the CD4-to-CD8 ratio occurred in the thymus and lymph nodes, coinciding with the highest thymus-to-body weight ratio and gradual increase in mature thymocytes expressing a pan-T lymphocyte marker. CONCLUSIONS: Postnatal thymopoiesis in the domestic cat favors production of mature CD8+ T lymphocytes over CD4+ T lymphocytes. This coincides with the emergence of CD8+ lymphocytes in the lymph node and precedes a more gradual increase in CD8+ cells in the blood. Therefore, the ontogeny of these effectors of cell-mediated immunity could be interrupted by infective agents that target lymphoid tissues of the neonate.

Aging↗
PubMed2005

The role of eye-associated lymphoid tissue in corneal immune protection.

Because the cornea is optimized for refraction, it relies on supporting tissues for moistening and nutrition and in particular for immune protection. Its main support tissue is the conjunctiva, in addition to the lacrimal gland, the latter which provides soluble mediators via the tear film. The cornea and conjunctiva constitute a moist mucosal surface and there is increasing evidence that apart from innate defence mechanisms, also lymphoid cells contribute to the normal homeostasis of the corneal surface. A Medline-based literature search was performed in order to review the existing literature on the existence, composition and functions of mucosa-associated lymphoid tissue (MALT) at the ocular surface for corneal protection. The existence of lymphoid cells at the ocular surface and appendage has been known for many years, but for a long time they were believed erroneously to be inflammatory cells. More recent research has shown that in addition to the known presence of lymphoid cells in the lacrimal gland, they also form MALT in the conjunctiva as conjunctiva-associated lymphoid tissue (CALT) and in the lacrimal drainage system as lacrimal drainage-associated lymphoid tissue (LDALT). Together this constitutes an eye-associated lymphoid tissue (EALT), which is a new component of the mucosal immune system of the body. When the topographical distribution of CALT is projected onto the ocular surface, it overlies the cornea during eye closure and is hence in a suitable position to assist the corneal immune protection during blinking and overnight. It can detect corneal antigens and prime respective effector cells, or distribute protective factors as secretory IgA.

Conjunctiva↗
PubMed1981

Binding of peanut lectin to thymic cortex and germinal centres of lymphoid tissue.

The binding pattern of horseradish peroxidase conjugated peanut lectin (HRP-PNL) on frozen sections of lymphoid tissue from man, mouse, rat, hamster, guinea-pig, rabbit, sheep and chicken has been investigated. Binding of PNL was found to be highly species dependent; man, mouse and sheep showed strong binding to lymphocytes in thymic cortex and germinal centres; lymphoid tissue from hamster, guinea-pig and rabbit did not stain with HRP-PNL and rat showed only lightly positive cells in thymic cortex and germinal centres; all lymphoid tissue from chicken, except the bursal cortex, bound PNL. Neuraminidase treatment of tissues which did not bind PNL resulted in strongly PNL-positive cells. Double binding studies on murine Peyer's patches with fluorescein isothiocyanate conjugated PNL (FITC-PNL) and tetramethylrhodamine isothiocyanate (TRITC)-anti-Thy-1.2 or anti-immunoglobulin reagents revealed 3%-10% of PNL positive cells to be Thy-1.2 positive and 70%-80% to bear surface immunoglobulin.

Agglutination↗
PubMed2002

Lymphoid tissues from patients with infectious mononucleosis lack monoclonal B and T cells.

In typical cases of infectious mononucleosis (IM), lymphoid tissue is rarely submitted for pathological examination. When lymphoid tissues from IM cases are examined, the histological appearance of IM may be difficult to distinguish from malignant lymphoma. The purpose of this study was to address the utility of clinical molecular assays for T and B cell clonality in distinguishing IM from lymphoid malignancy. DNA was recovered from paraffin-embedded archival lymphoid tissues of 18 cases of IM and 13 control cases representing other reactive lymphoid hyperplasias. T cell receptor gamma (TCR-gamma) and immunoglobulin heavy chain (IgH) gene rearrangements were assayed using our standard clinical polymerase chain reaction procedures targeting each of the four functional variable (V) families and the three joining (J) families of the TCR-gamma gene, and framework III of the IgH gene, respectively. In 17 of 18 cases of IM, no monoclonal T or B cell populations were detectable. One case, the only spleen specimen in the study, had an oligoclonal pattern of TCR-gamma rearrangements. The control cases representing other reactive hyperplasias also lacked monoclonality. The assays used were sensitive to clonal populations as small as 5% of cells. In this case series, no monoclonal lymphoid populations were identified in any case of IM. This finding suggests that molecular studies are useful in distinguishing IM from lymphoid neoplasms.

Adolescent↗
PubMed2002

Distribution and accumulation of PrP in gut-associated and peripheral lymphoid tissue of scrapie-affected Suffolk sheep.

The distribution of disease-associated prion protein (PrP) was investigated in eight animals (20-24 months of age) from a flock of Suffolk sheep that had experienced frequent cases of natural scrapie over a period of several years. Tissue from the central nervous system (CNS), alimentary tract, peripheral nervous system and lymphoreticular system was examined by histopathology and immunohistochemistry. The lymphoid tissues were subjected further to histoblot and immunofluorescence examination. The four clinically affected PrP(ARQ/ARQ) sheep had widespread accumulations of disease-associated PrP in the CNS, lymphoreticular system and peripheral ganglia. In the two PrP(ARQ/ARQ) sheep that did not show clinical signs of scrapie, only limited vacuolation and PrP accumulation were detected in the brain, but the results from the lymphoreticular system and peripheral nervous system were comparable with the clinically affected animals. The remaining PrP(ARR/ARR) and PrP(ARR/ARQ) sheep did not show proteinase K-resistant PrP accumulations in the lymphoid tissues examined and immunohistochemistry did not reveal the presence of disease-associated PrP. In lymphoid tissues of the PrP(ARQ/ARQ) sheep, the dominant localization of disease-associated PrP was in lymphoid nodules and double immunofluorescence labelling for PrP and CD21 provided further support for the role of follicular dendritic cells in scrapie in sheep. A striking finding in the present study was the large accumulations of disease-associated PrP in the lymphoid nodules of the alimentary tract at the late sub-clinical and clinical stage of the infection. The study also identified disease-associated PrP in extra-nodular sites of lymphoid tissues, such as the marginal zone of the spleen, and these observations were used to argue that cells of the mononuclear phagocyte system of sheep may be involved in the uptake, transport, elimination and shedding of the scrapie agent.

Animals↗