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A G Farr

Publications and source records attributed to A G Farr.

At least 73 records · Page 4Linked to original sources
PubMed1987

Expression of Ia antigens by murine kidney epithelium after exposure to streptozotocin.

In the normal murine kidney, Ia antigens are expressed by dendritic cells located within the interstitial connective tissue and scattered cells within the glomerulus. After receiving multiple low doses of streptozotocin, a nitrosourea derivative of glucose, kidney epithelium labeled intensely with anti-Ia antibodies. Ultrastructural immunohistochemistry indicated that the epithelial cells of the proximal convoluted tubules expressed Ia antigens on their basolateral surfaces while remaining Ia- on their luminal surfaces. This response to streptozotocin does not appear to be related to the diabetogenic potential of the drug, because BALB/cJ mice, which remain normoglycemic after treatment with streptozotocin, also exhibited strongly Ia+ tubular epithelium after treatment with streptozotocin.

Animals↗
PubMed1986

Evaluation of ricin A-chain immunotoxins directed against human T cells.

We have synthesized four immunotoxins (ITs) by covalently coupling the A chain of ricin to murine monoclonal antibodies that recognize surface antigens on human T cells. Treatment of human peripheral blood lymphocytes with either 10.2-A, directed against the CD5 (Tp67) antigen, or 64.1-A, directed against the CD3 (Tp19) antigen, abolished protein synthesis in cells subsequently cultured with phytohemagglutinin (PHA). In contrast, two other ITs (9.6-A and 35.1-A), both directed against the CD2 (Tp50) antigen, had minimal effects on protein synthesis in PHA-stimulated cells. The binding of each IT to T cells was shown by immunofluorescence with fluorescein-conjugated goat anti-mouse immunoglobulin (FITC-GAMIg) and fluorescein-conjugated rabbit anti-ricin A-chain (FITC-RAR) antibodies. Activity of the ricin A chain in each IT was demonstrated by its ability to inhibit protein synthesis in a cell-free reticulocyte lysate assay. Ultrastructural immunoperoxidase analysis of IT internalization showed that ineffective and effective ITs were endocytosed at the same rate (50% of cells had labeled endosomes after 15 min). However, ineffective IT 35.1-A was more rapidly delivered to lysosomes (15-30 min) than effective ITs (10.2-A and 64.1-A) (greater than or equal to 30 min). The data support the hypothesis that there are several distinct pathways for internalization of ITs and that the ability of ricin A chain to reach and inactivate ribosomes may depend upon the specific membrane receptor involved in binding a given IT, its route of internalization, and the rate of entry of the IT into lysosomes.

Antibodies, Monoclonal↗
PubMed1986

Isolation of murine thymic epithelium and an improved method for its propagation in vitro.

A reliable and reproducible method for the isolation and propagation of thymic epithelial cells is described. Thymic epithelial cells from enzymatically dissociated thymus stroma are first enriched by separation on a discontinuous Percoll density gradient. The cell fractions enriched for epithelial cells are then cultured with irradiated fibroblasts in Ham's F-12 nutrient medium. Colonies of cells in these cultures contain keratin and exhibit morphologic characteristics of epithelial cells. When subcultured, the epithelial cells no longer require irradiated fibroblasts as filler cells. Some of the epithelial cells in vitro retain expression of class II (Ia) major histocompatibility antigens. The generation of defined cultures of thymic epithelial cells promises to be useful in defining their role in T cell differentiation.

Animals↗
PubMed1986

Ontogeny of Langerhans cells in human embryonic and fetal skin: expression of HLA-DR and OKT-6 determinants.

Langerhans cells (LCs) have been identified in human skin by 10 weeks estimated gestational age (EGA), but it was not known when they first enter the epidermis or acquire HLA-DR, OKT-6, and ATPase reactivity. We assayed for LCs in human embryonic and fetal skin by using immunolabeling and histochemical techniques on epidermal sheets. HLA-DR+ and ATPase+ LCs were present in the epidermis by 6-7 weeks EGA, the youngest tissue examined. Most LCs were OKT-6- until about 12 weeks EGA when they underwent a dramatic increase in OKT-6 reactivity. Although LC densities between 50-100 days were statistically similar (100 cells/mm2 of epidermis), LCs early in development were smaller, less dendritic, and phenotypically heterogeneous. We conclude that LCs migrate into the epidermis during the first trimester and resemble the adult phenotype by the second trimester, long before the immune system is fully activated.

Adenosine Triphosphatases↗
PubMed1985

Expression of antigen-specific, major histocompatibility complex-restricted receptors by cortical and medullary thymocytes in situ.

We have examined the distribution of the antigen-specific, major histocompatibility complex-restricted receptor on mouse thymocytes in situ, using immunohistochemical techniques and the monoclonal antibody KJ16-133. This antibody reacts with the beta chain of the receptors on about 20% of peripheral murine T cells. Of the cortical thymocytes reacting with KJ16-133, cells with only cytoplasmic staining were most frequently observed. Such cytoplasmic staining was not observed in the medulla. Occasional cortical cells had low levels of surface expression, which was almost invariably patched in the region of contact with epithelial cell processes. KJ16-133+ medullary thymocytes had high levels of uniform surface labeling. These results suggest that thymic selection of MHC restriction and/or tolerance may occur in the cortex, where the receptors on maturing thymocytes interact with MHC proteins on epithelial cells.

Animals↗
PubMed1985

Light and electron microscopic studies on the localization of steroid-binding protein (SBP) in rabbit spermatozoa.

Light (fluorescence) and electron microscopic studies were carried out to localize steroid-binding protein (SBP) in rabbit spermatozoa. Both nonpermeabilized and permeabilized (with Tween 20, saponin, or cold acetone) spermatozoa showed fluorescence following treatment with antirabbit SBP (anti-rSBP) and subsequently with rabbit antisheep immunoglobulin G-fluorescein isothiocyanate. While the ejaculated spermatozoa were positive, epididymal sperm were observed to be negative. Although the pattern of localization of rSBP was variable, the occurrence of a negative equatorial region as well as the presence of an intense positive spherical profile ("spot") at the junction of the head and midpiece were notably consistent. The intensity of labeling with the probe, both at light and electron microscopic level, was maximal following permeabilization with cold acetone. A possible role of SBP as a steroid carrier protein across the plasma membrane of the sperm has been suggested.

Animals↗
PubMed1985

In situ ultrastructural demonstration of cells bearing Ia antigens in the murine pancreas.

Although an important role has been postulated for class II major histocompatibility gene products in the rejection of transplanted islets, the identity of the cells bearing these molecules within pancreatic tissue has been the topic of some controversy. To clearly define the cell population(s) within the murine pancreas that express Ia antigens, perfused murine pancreata were processed for the ultrastructural in situ demonstration of Ia antigens. It was found that Ia antigen expression was restricted to mononuclear cells adjacent to capillaries throughout the exocrine and endocrine portions of the pancreas. Vascular endothelium and ductular epithelium did not express detectable amounts of Ia antigens.

Animals↗
PubMed1985

Epithelial heterogeneity in the murine thymus: fucose-specific lectins bind medullary epithelial cells.

By means of histochemical techniques, two lectins with nominal specificity for L-fucose, Tetragonolobus purpureas agglutinin (TPA), and Ulex europeus agglutinin (UEA) were found to specifically label the medullary area of murine thymuses. Although the binding of both lectins was restricted to the medullary area of the thymus, each staining pattern was unique. Cells binding UEA formed a reticular network throughout the medulla, whereas cells binding TPA occurred as single cells or small clumps of cells and resembled Hassall's corpuscles. The cells binding either lectin were identified as epithelial on the basis of ultrastructural features (tonofilaments, desmosomes, and keratohyalin bodies) and resembled Ia+ medullary epithelial cells described previously. An age-related decline in UEA binding was observed, whereas labeling with TPA remained unchanged. On the basis of the labeling patterns obtained with UEA and TPA and the reported specificities of these two lectins, it is suggested that the majority of the fucose detected is associated with type 1 carbohydrate chains.

Aging↗
PubMed1984

Reduced expression of Ia antigens by thymic epithelial cells of aged mice.

Thymic Ia antigen expression was examined with biochemical and immunohistochemical techniques. We found that expression of Ia antigens was reduced in thymic tissue of aged mice and that much of this loss was associated with cortical thymic epithelial cells. The ontologic pattern of Ia antigen expression in the thymus closely followed that observed for thymic weight, reaching maximal values at 4 wk of age and declining thereafter.

Aging↗
PubMed1983

Cells bearing Ia antigens in the murine thymus. An ultrastructural study.

Light- and electron-microscopic immunohistochemical examination of the murine thymus revealed that epithelial cells throughout the thymus expressed Ia antigens, as did interdigitating cells, monocytes, and macrophages located in perivascular "cuffs" associated with corticomedullary and medullary blood vessels. Thymic lymphocytes also expressed Ia antigens, but only at areas of contact with Ia-positive nonlymphoid cells. We observed evidence for synthesis of Ia antigens by epithelial cells, but not by thymic lymphocytes. These data indicate that several morphologically distinct populations of cells in the thymus express Ia antigens and thus may be involved in cellular interactions regulating I-region-restricted T-lymphocyte differentiation.

Animals↗
PubMed1980

The structure of the sinus wall of the lymph node relative to its endocytic properties and transmural cell passage.

The internal structure of cells lining the lymphatic sinus of the lymph node includes the presence of large bristle-coated vesicles, transfer tubules, and vesicular organelles for the uptake and intracellular disposition of endocytosed material. The lining cells of the sinuses phagocytose particulate material from the lymph in the same manner as the sinusoidal endothelium of the bone marrow takes up particulates from the blood and, thus, are similar in this respect to the endothelial lining of the bone marrow sinusoids. Transmission and scanning electron microscopic examination of the lymphatic sinus wall in rat lymph nodes show that the walls of the lymphatic sinuses are continuous and do not have permanent apertures allowing free communication between the extrasinusoidal and intrasinusoidal compartments in the lymph node. Migrating lymphocytes cross the lymphatic sinus wall intracellularly, i.e., through the body of the lining cell, by making a temporary migration pore, which closes after the cell has reached the lumen of the sinus. In addition there are sporadic aggregations of macrophages in transmural positions. The direction of their movement is unknown.

Animals↗
PubMed1979

Macrophage-T cell interactions involving Listeria monocytogenes--role of the H-2 gene complex.

This study reports on the in vitro interactions between T cells from Listeria-immunized mice, macrophages from normal mice, and heat-killed Listeria organisms. This interaction was assayed either by determing the amount of thymocyte mitogen in culture fluids after 24 hr, or by estimating the degree of T cell proliferation after 96 hr. Each assay depended on critical concentrations of macrophages, T cells, and heat-killed Listeria, points that were evaluated in a number of experiments. Both assays required specific Listeria-immune T cells. For an effective interaction, the T cells and the macrophages had to share the I-A region of the H-2 gene complex. Macrophages bearing Ia, which represented a minor population of macrophages, were essential for the proliferative response to macrophage-associated Listeria. Also, Ia-bearing macrophages were an important component in the interactions leading to increased secretion of mitogen. The immunogenic moiety associated with Listeria was short-lived, disappearing 24 hr after uptake of Listeria by macrophages. The interactions were not blocked by anti-Listeria antibodies but were partially sensitive to trypsinization.

Animals↗
PubMed1978

Regulation of lymphocyte proliferation and differentiation by macrophages.

In this paper, we consider the role of a macrophage secretory product in promoting thymocyte differentiation, as well as a macrophage-immune T cell interaction that results in augmented secretion of lymphostimulatory factors. When cultured with the thymocyte-differentiating factor (TDF), thymocytes show a physiological increase in H-2D and K, decreased sensitivity to lysis with anti-TL and complement, and acquisition of responsiveness in the mixed lymphocyte culture. Development of the mature phenotype requires 2 to 3 days of culture and, once attained, is stable. The induced antigenic changes do not require cell division. The activity demonstrated by TDF, which is not attributable to interferon and cannot be replaced by 2-mercaptoethanol, is also displayed by normal thymic macrophages themselves. Enhanced secretion of TDF and of a distinct mitogenic protein follows the interaction of macrophages and immune T cells. This interaction is shown to require physical contact of the two cell types and is regulated by products of the I-A region of the major histocompatibility complex.

Animals↗
PubMed1977

Secretion of mediators following T lymphocyte-macrophage interaction is regulated by the major histocompatibility complex.

In this study we show that T cells from mice infected with Listeria monocytogenes can interact in vitro with normal macrophages to produce a number of soluble mediators, including lymphostimulatory molecules. One of these molecules was a 15,000-dalton protein mitogenic for thymocytes. Generation of mitogenic activity was essentially completed by the first 24 hr of culture and did not require the addition of Listeria antigens. Production of mitogenic protein required contact between the lymphocytes and macrophages, because it did not occur when the two cells were separated by a cell-impermeable membrane. Optimal production of mitogenic protein occurred only when the lymphocytes and macrophages shared homologous I-A regions of the major histocompatibility complex. Once generated, the mitogenic protein did not display histocompatibility restriction and could stimulate allogeneic as well as syngeneic thymocytes. Strains of mice with the C57 background responded poorly to mitogenic protein even though those strains were capable of producing it. We conclude that an early stage in T cell immunity to Listeria involves an intimate association with macrophages regulated by the H-2 complex.

Animals↗
PubMed1975

The mode of lymphocyte migration through postcapillary venule endothelium in lymph node.

The pathway of migration of lymphocytes across the walls of the postcapillary venules was studied in lymph nodes of rats. By means of serial sections, it was determined that lymphocytes enter the venule wall through the endothelial cells and not through the intercellular spaces. After the endothelial cell has been penetrated, the lymphocytes enter the intercellular spaces, from where they gain access to the lymphatic parenchyma. It cannot be excluded, however, that in some instances the path of migration of a lymphocyte is entirely through an endothelial cell from lumen to subendothelial space. While perforating an endothelial cell, a migrating lymphocyte may be in simultaneous contact with the vascular lumen, the intercellular space, and the subendothelial tissue.

Animals↗
PubMed1975

Macrophage-lymphocyte clusters in lymph nodes: a possible substrate for cellular interactions in the immune response.

The lumens of the lymphatic sinuses in lymph nodes are traversed by fibrocellular trabeculae. Joined to these trabeculae were macrophages, which formed cell clusters with lymphocytes. It is proposed, based on structural similarities, that these cell clusters are the equivalent in vivo to those seen during primary and secondary immune responses in vitro. These intraluminal macrophages were located in the path of lymph-borne antigen, as well as in the path of newly formed and recirculating lymphocytes in sinuses. This would facilitate the possible interaction between macrophage-associated antigen and antigen-reactive lymphoid cells. The attachment of numerous lymphocytes to the surfaces of macrophages and the resulting cell clusters also afford increased opportunities for lymphocyte-lymphocyte contact.

Animals↗