Journal of Experimental Medicine
0022-1007
1540-9538
Mỹ
Cơ quản chủ quản: ROCKEFELLER UNIV PRESS , Rockefeller University Press
Lĩnh vực:
Immunology and AllergyImmunologyMedicine (miscellaneous)
Phân tích ảnh hưởng
Thông tin về tạp chí
Since its inception in 1896, the goal of Journal of Experimental Medicine (JEM) has been to publish outstanding and enduring studies in medical biology. At a time when many leading publishing groups are establishing topic-specific journals, we believe it is critical to complement that approach by offering a distinguished venue for publication of studies that integrate disciplines within the field of pathogenesis.
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EXPERIMENTAL PLEURISY—RESOLUTION OF A FIBRINOUS EXUDATE Fibrinous pleurisy produced by a sterile inflammatory irritant offers opportunity for study of the part taken by enzymes of leucocytes in the resolution of a fibrinous exudate. When turpentine is injected into the subcutaneous tissue of the dog, an abscess results, but when an equal quantity of turpentine is injected into the pleural cavity, there is abundant exudation of coagulable fluid and the serous surfaces are covered by a layer of fibrin. Accumulation of fluid which can be followed during life by percussion of the animal's chest reaches a maximum at the end of three days, and then gradually subsides, so that at the end of six days, in most instances, the cavity contains no fluid. Fibrin, though diminished in amount at the time when fluid has been absorbed, is still present, and gradually disappears; at the end of two or three weeks the cavity has returned to the normal, save for a few organized adhesions.
Turpentine injected into the right pleural cavity may cause serofibrinous pleurisy on the left side; this inflammation may reach a maximum intensity at a time when pleurisy on the right side is subsiding.
During the early stage of inflammation fibrinous exudate, freed from the serum by washing in salt solution, undergoes digestion when suspended in an alkaline (0.2 per cent. sodium carbonate) or in an acid medium (0.2 per cent. acetic acid). At the end of five days, at a time when fluid is disappearing from the pleural cavity, digestion fails to occur in an alkaline medium, but occurs with much activity in the presence of acid.
During the first stage of the inflammatory reaction, when fluid is abundant and the fibrin which is present digests in alkali, thus indicating the presence of leucoprotease, polynuclear leucocytes are very numerous in the meshes of the fibrin. In the second stage, the exuded fibrin contains only one enzyme digesting in the presence of acid. At this time polynuclear leucocytes have disappeared and only mononuclear cells are embedded in the fibrin.
Products of proteolytic digestion, namely, peptone and albumose, absent in the exuded fluid during the first day or two days of inflammation, are present after three days and are found in less quantity at a later period.
The exuded fluid does not at any stage of the inflammatory reaction lose it spower to inhibit both enzymes contained in the leucocytes.
The exudate remains alkaline throughout the period of inflammation, but its alkalinity is less than that of the blood and diminishes slightly with the progress of inflammation.
Since the acids, which in vitro favor the action of the enzyme, present alone during the second stage of the inflammatory reaction, do not occur in the body, the possibility has suggested itself that carbon-dioxide brings this enzyme into action. If carbon-dioxide is passed through normal salt solution in which strips of such fibrin are suspended, digestion is greatly hastened. The normal inhibition exerted by blood serum upon the enzyme is overcome by carbon-dioxide and in the presence of a small quantity of blood serum, carbon-dioxide causes greater enzymotic activity than in the presence of salt solution alone.
Tập 9 Số 4 - Trang 391-413 - 1907
Human T Cell Receptor γδ Cells Recognize Endogenous Mevalonate Metabolites in Tumor Cells T lymphocytes expressing the T cell receptor (TCR)-γδ recognize unknown antigens on tumor cells. Here we identify metabolites of the mevalonate pathway as the tumor ligands that activate TCR-γδ cells. In tumor cells, blockade of hydroxy-methylglutaryl-CoA reductase (HMGR), the rate limiting enzyme of the mevalonate pathway, prevents both accumulation of mevalonate metabolites and recognition by TCR-γδ cells. When metabolite accumulation is induced by overexpressing HMGR or by treatment with nitrogen-containing bisphosphonate drugs, tumor cells derived from many tissues acquire the capacity to stimulate the same TCR-γδ population. Accumulation of mevalonate metabolites in tumor cells is a powerful danger signal that activates the immune response and may represent a novel target of tumor immunotherapy.
Tập 197 Số 2 - Trang 163-168 - 2003
Human intestinal Vdelta1+ lymphocytes recognize tumor cells of epithelial origin. gammadelta T cells can be grouped into discrete subsets based upon their expression of T cell receptor (TCR) variable (V) region families, their tissue distribution, and their specificity. Vdelta2+ T cells constitute the majority of gammadelta T cells in peripheral blood whereas Vdelta1+T cells reside preferentially in skin epithelium and in the intestine. gammadelta T cells are envisioned as first line host defense mechanisms capable of providing a source of immune effector T cells and immunomodulating cytokines such as interleukin (IL) 4 or interferon (IFN) gamma. We describe here the fine specificity of three distinct gammadelta+ tumor-infiltrating lymphocytes (TIL) obtained from patients with primary or metastatic colorectal cancer, that could be readily expanded in vitro in the presence of IL-1beta and IL-7. Irrespective of donor, these individual gammadelta T cells exhibited a similar pattern of reactivity defined by recognition of autologous and allogeneic colorectal cancer cells, renal cell cancer, pancreatic cancer, and a freshly isolated explant from human intestine as measured by cytolytic T cell responses and by IFN-gamma release. In contrast, tumors of alternate histologies were not lysed, including lung cancer, squamous cell cancer, as well as the natural/lymphocyte-activated killer cell-sensitive hematopoietic cell lines T2, C1R, or Daudi. The cell line K562 was only poorly lysed when compared with colorectal cancer targets. Target cell reactivity mediated by Vdelta1+ T cells was partially blocked with Abs directed against the TCR, the beta2 or beta7 integrin chains, or fibronectin receptor. Marker analysis using flow cytometry revealed that all three gammadelta T cell lines exhibit a similar phenotype. Analysis of the gammadelta TCR junctional suggested exclusive usage of the Vdelta1/Ddelta3/Jdelta1 TCR segments with extensive (< or = 29 bp) N/P region diversity. T cell recognition of target cells did not appear to be a major histocompatibility complex restricted or to be correlated with target cell expression of heat-shock proteins. Based on the ability of some epithelial tumors, including colorectal, pancreatic, and renal cell cancers to effectively cold target inhibit the lysis of colorectal cancer cell lines by these Vdelta1+ T cell lines, we suggest that intestinal Vdelta1+ T cell lines, we suggest that intestinal Vdelta1+ T cells are capable of recognizing cell surface Ag(s) shared by tumors of epithelial origin.
Tập 183 Số 4 - Trang 1681-1696 - 1996
PERSISTENT ANTIGENIC VARIATION OF INFLUENZA A VIRUSES AFTER INCOMPLETE NEUTRALIZATION IN OVO WITH HETEROLOGOUS IMMUNE SERUM Antigenic variants of influenza A virus strains emerge on serial passage in ovo in the presence of immune serum against different but related strains. An old laboratory strain (PR8) which had been through hundreds of animal passages was as readily modified by this procedure as recently recovered strains. Such variants apparently can be obtained at will and show antigenic patterns which are reproducible and appear to be predictable in terms of the immune serum used for their selection. Variant strains retain their new antigenic patterns on serial passage in ovo in the absence of immune serum. Limited serial passage in ovo of strains in the absence of immune serum did not result in the emergence of antigenic variants. Similarly, serial passages of strains in ovo in the presence of immune serum against widely different strains, which failed to show significant cross-neutralization, did not lead to the appearance of antigenic variants.
Tập 92 Số 5 - Trang 441-462 - 1950
LEUKOCYTE-DEPENDENT HISTAMINE RELEASE FROM RABBIT PLATELETS We have studied the leukocyte-dependent mechanism of histamine release (LDHR) from rabbit platelets, a complement-independent mechanism which has been implicated in the deposition of immune complexes in acute serum sickness of rabbits. It was found by chromatography and passive transfer of serum from immunized rabbits that the antibody responsible for the LDHR was of IgE type. By electron microscope study of the reaction, the leukocyte involved in agglutination of platelets and release of their histamine content was identified as the basophil. Upon addition of antigen, basophils sensitized with IgE degranulated, released their histamine content and a platelet-activating factor (PAF) that caused aggregation of platelets and release of their histamine. Conditions of preparing and preserving PAF activity and some properties of this factor have been elucidated. LDHR must, therefore, be considered as an immediate hypersensitivity-type mechanism which may link allergic reactions with immunologic disease associated with severe structural injury.
Tập 136 Số 6 - Trang 1356-1377 - 1972
Surface antigens of malaria merozoites. A high molecular weight precursor is processed to an 83,000 mol wt form expressed on the surface of Plasmodium falciparum merozoites. A technique was developed for obtaining high yields of naturally released Plasmodium falciparum merozoites from synchronous cultures of parasitized erythrocytes. The cultured erythrocytes were treated with trypsin to prevent reinvasion (6), and the released merozoites that accumulated extracellularly were harvested by differential centrifugation. The total biosynthetically labeled proteins of schizonts and merozoites, and those immunoprecipitated by human immune serum were analyzed and compared. The surface antigens of free merozoites, labeled by lactoperoxidase-catalyzed iodination, were also described. A monoclonal antibody, specific for a 195,000 mol wt schizont protein, and processing fragments derived from it (3) were used in immunoprecipitation and Western transfer analyses to determine which of the processing fragments are associated with merozoites and which of them are located on the merozoite surface. It was found that processing of the 195,000 mol wt precursor down to an 83,000 mol wt fragment is complete in free merozoites, and that this fragment is expressed as one of the major surface antigens of P. falciparum merozoites.
Tập 158 Số 5 - Trang 1647-1653 - 1983
THE REQUIREMENT OF MORE THAN ONE ANTIGENIC DETERMINANT FOR IMMUNOGENICITY Rabbits primarily stimulated with a BSA (bovine serum albumin)-sulfanilic acid complex will produce a good secondary response to the sulfanilic acid hapten if the carrier used in the secondary stimulus is again BSA, and not if the secondary carrier is HGG (human gamma globulin). In the latter situation, a good secondary response is obtained, however, if the rabbits are pretreated a few weeks earlier with free HGG. We conclude that the immune stimulus involves the recognition of carrier determinants unrelated to the hapten.
As the receptors for recognition of unrelated determinants are probably situated on different cells, we suggest that the immune stimulus leading to antibody formation requires the interaction of two antigen-bridged cells.
Tập 129 Số 6 - Trang 1131-1143 - 1969
CELL TO CELL INTERACTION IN THE IMMUNE RESPONSE The number of discrete hemolytic foci and of hemolysin-forming cells arising in the spleens of heavily irradiated mice given sheep erythrocytes and either syngeneic thymus or bone marrow was not significantly greater than that detected in controls given antigen alone. Thoracic duct cells injected with sheep erythrocytes significantly increased the number of hemolytic foci and 10 million cells gave rise to over 1000 hemolysin-forming cells per spleen. A synergistic effect was observed when syngeneic thoracic duct cells were mixed with syngeneic marrow cells: the number of hemolysin-forming cells produced in this case was far greater than could be accounted for by summating the activities of either cell population given alone. The number of hemolytic foci produced by the mixed population was not however greater than that produced by an equivalent number of thoracic duct cells given without bone marrow. Thymus cells given together with syngeneic bone marrow enabled irradiated mice to produce hemolysin-forming cells but were much less effective than the same number of thoracic duct cells. Likewise syngeneic thymus cells were not as effective as thoracic duct cells in enabling thymectomized irradiated bone marrow-protected hosts to produce hemolysin-forming cells in response to sheep erythrocytes.
Irradiated recipients of semiallogeneic thoracic duct cells produced hemolysin-forming cells of donor-type as shown by the use of anti-H2 sera. The identity of the hemolysin-forming cells in the spleens of irradiated mice receiving a mixed inoculum of semiallogeneic thoracic duct cells and syngeneic marrow was not determined because no synergistic effect was obtained in these recipients in contrast to the results in the syngeneic situation. Thymectomized irradiated mice protected with bone marrow for a period of 2 wk and injected with semiallogeneic thoracic duct cells together with sheep erythrocytes did however produce a far greater number of hemolysin-forming cells than irradiated mice receiving the same number of thoracic duct cells without bone marrow. Anti-H2 sera revealed that the antibody-forming cells arising in the spleens of these thymectomized irradiated hosts were derived, not from the injected thoracic duct cells, but from bone marrow.
It is concluded that thoracic duct lymph contains a mixture of cell types: some are hemolysin-forming cell precursors and others are antigen-reactive cells which can interact with antigen and initiate the differentiation of hemolysin-forming cell precursors to antibody-forming cells. Bone marrow contains only precursors of hemolysin-forming cells and thymus contains only antigen-reactive cells but in a proportion that is far less than in thoracic duct lymph.
Tập 128 Số 4 - Trang 821-837 - 1968
THE CYTOLOGICAL DISTRIBUTION IN PIGEON SKELETAL MUSCLE OF ENZYMES ACTING ON PHOSPHORYLATED NUCLEOTIDES A procedure has been described for the centrifugal fractionation of the cytological components of pigeon breast muscle. An analysis of the distribution of enzyme activity among the different particles reveals a predominant location of magnesium-activated ATPase and myokinase in the cytochondria. The myofibrillar nuclear components are the site of calcium-activated ATPase and adenylic acid deaminase.
Tập 97 Số 4 - Trang 553-572 - 1953
Interaction of glucocorticoids with macrophages. Identification of glucocorticoid receptors in monocytes and macrophages. Glucocorticoid binding was measured in resident and thioglycollate-elicited mouse peritoneal macrophages, rabbit alveolar macrophages, and human monocytes. Two assays of binding were used--an assay with intact cells in suspension or monolayers, and an assay of cytosol and nuclear forms of glucocorticoid receptors. The mononuclear phagocytes contained approximately equal to 4--10 X 10(3) high affinity receptor sites per cell, with dissociation constants of approximately equal to 2--8 nM dexamethasone. The binding to the saturable sites was specific for steroids with glucocorticoid or antiglucocorticoid activity. Cortisol, corticosterone, and progesterone competed with dexamethasone for binding, whereas estradiol, dihydrotestosterone, and 11-epicortisol competed very little. Binding of dexamethasone to cytosol and nuclear forms of the receptor complex and temperature-sensitive translocation of cytosol forms to nuclear forms were shown. At 37 degrees C the predominant form of the hormone-receptor complex was nuclear. These results demonstrate that corticosteroids interact with macrophages at physiological concentrations.
Tập 147 Số 6 - Trang 1684-1694 - 1978