Aggregates Of Lymphoid Cells Research Articles

Histopathological changes in Newcastle disease affecting racing pigeons in Japan.

Newcastel disease (ND) occurred among flocks of racing pigeons in Japan from 1983 to 1984. Diseased pigeons exhibited nervous symptoms and diarrhea with a 13% of mortality rate. Thirty-three of the affected pigeons from 9 flocks were subjected to pathological examination. No characteristic gross changes were observed. In 15 of the 33 pigeons including 10 birds (group 1) from which ND viruses (NDV) were isolated and 5 affected birds (group 2) which had no hemagglutination-inhibition (HI) antibodies and in which no attempt was made to isolate NDV, the main histopathological changes consisted of necrosis or atrophy of the lymphoid tissue in the spleen as well as in the bursa of Fabricius and thymus, splenitis, nephritis, and hepatitis, in addition to non-purulent encephalomyelitis. In the others (18 of 33 pigeons; group 3) in which HI antibodies were detected but NDV was not isolated, the lesions consisted of hyperplasia of the lymphoid tissue in the spleen, follicular aggregation of lymphoid cells in the kidney and non-purulent encephalomyelitis. Based on the histopathological changes, it was considered that the viscerotropic and neurotropic strains of NDV had affected flocks of racing pigeons in Japan.

Heparin‐induced aggregation of lymphoid cells

The effects of different carbohydrates on cell-to-cell adhesion were examined in an aggregation assay, which consisted of swirling a suspension of cells and monitoring the loss of single cells with a Coulter Counter. Of the carbohydrates tested, only heparin and dextran sulfate induced cell aggregation. This effect occurred in freshly isolated mouse splenocytes and in cultured cells of lymphoid origin (P388, YAA-CI) but not in cell lines of fibroblastic origins (3T3, SV-3T3, BHK, and PY-BHK). Using the YAA-CI cell line for further study, we found that aggregation could be induced by relatively small amounts of heparin (less than 10 micrograms/ml). Binding experiments with 3H-heparin showed that under normal physiological conditions each YAA-CI cell bound approximately 2 X 10(6) molecules of heparin at saturation with a Kd of 3.5 X 10(-7) M. This binding was blocked by both unlabelled heparin and dextran sulfate but not by other carbohydrates. When the pH of the medium was decreased, the heparin-induced aggregation was inhibited, and the Kd of the 3H-heparin binding was increased. In a similar fashion, when the ionic strength of the medium was increased, heparin-induced aggregation was inhibited and the Kd of the interaction was increased. These results suggest that the aggregation is inversely related to the Kd of the interaction and that the binding of heparin to the cell surface is primarily of an ionic nature.

A collision analysis of lymphoid cell aggregation

We have obtained data on the frequency of aggregates of different size classes and on the maximum aggregate diameter of lymphoid cells subjected to aggregation in the laminar shear field of a Couette viscometer. Maximum aggregate diameter reached a plateau level during aggregation. This plateau is considered to be the result of a balance between the hydrodynamic shear forces tending to resist the formation of aggregates, and the adhesive forces of the aggregated cells tending to resist dissociation. Stepwise-increases in the shear rate produced aggregates of progressively smaller maximum diameter until the limiting (i.e. control equivalent) diameter was reached. Equations governing these stepwise changes in aggregate diameter were obtained by regression analysis, and an estimate of the force of dissociation (FD) was made from derived values of the critical shear rate. Thymocytes (FD=2.54 X 10(-6) N m-2/cell) were found to be more adhesive than lymphocytes (FD=2.05 X 10(-6) N m-2/cell), in agreement with current concepts. The observed data on aggregate frequency were seen to be of poor fit with a model of aggregation derived by collision analysis of the aggregation process. This led us to consider the possibility that all cells may not share the same probability of forming an adhesion. We thus derived further models of aggregation in which some fraction of the total cells was considered to have enhanced possibilities of a collision producing an adhesion. Of the models we considered, a 15% preferred fraction offered best agreement with the experimental observations. We therefore conclude that the populations of cells studied in this report are not 'homogenous' in that some cells are more adhesive than others. Alterations in the percentage of the preferred fraction of cells will lead to different aggregate-frequency indices. Such changes might be expected to occur during the initial stages of carcinoma development.

HISTOLOGICAL CHANGES IN THE SUBMANDIBULAR GLANDS OF RATS AFTER INTRADUCTAL INJECTION OF CHEMICAL CARCINOGENS

Carcinogens injected into the excretory canal of submandibular gland of Donryu rats revealed the following histologic changes in salivary glands. 20-Methylcholanthrene induced squamous cell metaplasia, fibrosis in the early stages, and "benign lymphoepithelial lesion"-like pattern after 3 months. Dense hyalinization occurred after 4-5 months with so-called "mixed tumor"-like pattern. In the later stages epidermoid carcinoma and fibrosarcoma were observed. 9, 10-Dimethylbenzanthracene caused degenerative change, metaplasia, fibrosis and cell infiltration, and later carcinoma and sarcoma appeared at a high rate. 4-Nitroquinoline-N-oxide led to dense hyalinization and so-called "mixed tumor"-like pattern was observed in many specimens. N-nitroso-N-methyl urethane and N-methyl-N-nitroso-N'-nitroguanidine revealed metaplastic changes, fibrosis and lymphoid infiltration. Scarlet red induced remarkable infiltration and aggregation of lymphoid cells, showing benign "lymphoepithelial lesion"-like pattern.

Interactions between Marek's disease herpesvirus and avian leucosis virus in tissue culture.

A GROUP B herpesvirus is important in the aetiology of Marek's disease, a highly contagious lymphoproliferative disease of chickens1,2. Chicks inoculated with enveloped Marek's disease herpesvirus (MDHV), extracted from feather follicle epithelium of chickens with the disease, developed tumour-like aggregates of lymphoid cells in the viscera and frequently in the peripheral nerves3,4. Cultures of chicken embryo fibroblast (CEF) cells infected with MDHV develop discrete foci of altered cells5. Our data show that MDHV infection of cultures of CEF cells, previously infected with an avian leucosis virus (RAV-2), results in both a reduction in the number of MDHV foci and an increase in the complement fixing avian leucosis antigen (COFAL)6 titre.

Cellular interactions and the secondary response in vitro.

ALTHOUGH the role of cellular cooperation in the induction of the immune response has become firmly established only recently1, morphological evidence suggesting that such cooperation takes place is quite old. Reports2 of the aggregation of lymphoid cells around macrophages3 have been confirmed: “islets”, “rosettes” or “clusters” in cultures of cells (derived from humans4, guinea-pigs5, rabbits6 or mice7) stimulated with antigen or PHA8 were reported. We have investigated cluster formation to ascertain its relationship, if any, to the antigen-induced stimulation of sensitized cells9. We used peripheral blood leucocytes from rabbits immunized to bovine serum albumin (BSA) or to human red blood cells (HRBC). The BSA was given in complete Freund's adjuvant (three intramuscular injections of 7.5 mg BSA each, into the hind legs at weekly intervals). HRBC (1 ml.) was given once into the ear vein, as a 20% suspension in saline. Cell cultures and 3H-thymidine incorporation were measured as before10. To prepare cell smears, cells were washed three times and suspended in one drop of normal rabbit serum and 1 µl. of the suspension was spread on a microscope slide. This ensured a reasonably constant number of cells per slide and made possible comparisons between different experiments. Smears were fixed with methanol and stained with Giemsa.

Cellular hypersensitivity in the cornea. An analysis of the limbus and limbal cellular infiltration by light and electron microscopy.

Guinea pigs with cellular (delayed) hypersensitivity to the protein ferritin and to bacille calmette Guerin (BCG) vaccine were challenged intracorneally. Clinically and by light microscopy, the timing of the response and the character of the cellular infiltrate were similar in both instances. An electron microscopic study was made of the limbus and limbal cell population at varying times following challenge in the ferritin-sensitized animals. Quantitative analysis of the cell population at the limbus was made, and several features of the response have been emphasized. Characteristics of the reaction were: the presence of large numbers of histiocytes early in the reaction; intercellular edema and inflammation of the conjunctival epithelium; nodular aggregates of lymphoid cells; and the small number of activated lymphoid elements present. These findings were discussed and related to known mechanisms of cellular hypersensitivity.

The Thymus. Its Role in Immune Responses, Leukaemia Development and Carcinogenesis, vol 5.

The thymus, long considered a useless vestige, has in recent years become significant. It is an exciting renaissance involving cytokinetics, humoral control, immune response, autoimmunity, leukemia, and carcinogenesis. Metcalf, a solid contributor to this knowledge, assembles critical observations from his and other laboratories and constructs a concise account of present knowledge and thinking about this organ. In this account, the unfolding of perceptive hypotheses and ingenious experiments is as fascinating as are the individual items of knowledge, per se. The thymus consists of a loose framework of epithelial and reticulum cells (arising from local anlage) in which dense aggregates of lymphoid cells (arising largely from other body sites) are found. Intense mitotic activity occurs in lymphocytes adjacent to some framework cells. About 99% of lymphocytes die in situ after an intrathymic lifespan of three or four days. Despite this graveyard function, the thymus appears important in regulation of lymphocyte levels

CONTACT-INDUCED CYTOTOXICITY BY LYMPHOID CELLS CONTAINING FOREIGN ISOANTIGENS.

In tissue culture, immune lymph node cells containing foreign histocompatibility antigens of the H-2 type exert marked cytotoxic effects on tumor cells incompatible with the H-2 antigen. An equally pronounced effect is obtained when normal allogeneic and semi-isologous lymphoid cells of F(1) hybrids are caused to aggregate around the target tumor cells by treating the cultures with either heat-inactivated rabbit antiserum to mouse cells or phytohemagglutinin. Isologous lymph node cells have no effect. Thus, aggregation of lymphoid cells and target cells is a necessary but insufficient requirement for cytotoxicity in vitro; in addition, close contact must be established between histoincompatible cells.