bluuebunny/crossref_metadata_2025_split huggingface dataset:
PHAGOCYTOSIS OF IMMUNE COMPLEXES BY MACROPHAGES
Authors: Mantovani B. , Rabinovitch M. , Nussenzweig V. 
Published: June 2004

Sheep red cells (E) sensitized with IgG antibody (EA) or with antibody and complement (EAC) interact in vitro with mouse peritoneal macrophage monolayers. The role of IgG and of C3 in the attachment and ingestion of the erythrocytes was examined by means of quantitative technique utilizing 51Cr-labeled E. Controlled osmotic lysis permitted the separate measurement of the radioactivity associated with bound or with ingested E. IgG-125I was used to estimate the number of IgG molecules bound per E as a function of the IgG concentration. Control experiments showed that iodination did not influence the extent of binding of IgG to E and that the binding of IgG prepared from immune serum could be essentially ascribed to its anti-E antibody content. Only between 103 and 104 rabbit anti-E IgG molecules per erythrocyte were needed for detectable attachment and ingestion of EA (a maximum number of 6 x 105 IgG antibody molecules could be accomodated on one erythrocyte).
Evidence was obtained that C3 is primarily involved in particle attachment, whereas only IgG is able to markedly promote the ingestion of particles attached to macrophages: (a) Addition of complement to the EA substantially increased the binding to the macrophages, whereas ingestion was increased to a smaller extent. Both binding and ingestion of EAC were markedly inhibited by papain fragments of IgG obtained from a rabbit antiserum to mouse C3. (b) Low doses (2 µg/ml) of papain fragments of IgG from a rabbit antiserum to mouse IgG markedly reduced the ingestion of EAC, whereas attachment of EAC to macrophages was inhibited to a much smaller degree.
The possible relevance of these findings for the in vivo fate of particulate immune complexes as they interact with macrophages is discussed. It is suggested that in the primary immune response, when the complexes are predominantly in the form of EA (IgM) or EA (IgM) C3, they would tend to remain on the surface of the macrophages and thus be in a position to stimulate immunocompetent cells. In the secondary response, when EA (IgG) or EA (IgG) C3 predominate, the complexes would tend to be more rapidly interiorized and degraded by the mononuclear phagocytes,
MORPHOLOGICAL AND FUNCTIONAL STUDIES OF FETAL THYMUS TRANSPLANTS IN MICE
Authors: Biggar W. D. , Stutman Osias , Good Robert A. 
Published: June 2004

The fetal thymus at 13 days of gestation withstands transplantation and develops normally under the renal capsule of a syngenic host. Distinct differences were observed between the fetal thymus grafts and grafts from neonatal or adult thymus donors. The fetal thymus graft did not undergo the rapid and severe necrosis observed when adult thymus was grafted. Furthermore, when thymuses were transplanted into allogenic recipients, rejection was delayed.
The fetal thymus was as effective as the adult thymus in restoring syngenic neonatally thymectomized mice and far superior to adult thymus when grafted into allogenic recipients. These observations seem relevant to clinical efforts to restore immunocompetence in patients with congenital absence of the thymus.
IMMUNOPATHOGENESIS OF ACUTE CENTRAL NERVOUS SYSTEM DISEASE PRODUCED BY LYMPHOCYTIC CHORIOMENINGITIS VIRUS
Authors: Gilden Donald H. , Cole Gerald A. , Nathanson Neal 
Published: June 2004

Lymphocytic choriomeningitis (LCM) virus carriers were established by intracerebral inoculation of adult BALB/c mice followed by a single dose of cyclophosphamide (CY) (150 mg/kg) 3 days after infection, and by intracerebral injection within 24 hr of birth. These carriers were then adoptively immunized with spleen cells or serum from immune or normal BALB/c donors.
Transfer of immune spleen cells into drug-induced carriers consistently resulted in acutely fatal choriomeningitis, histologically strikingly similar to classical LCM. Normal spleen cells or immune serum failed to produce either central nervous system (CNS) pathology or illness with any regularity. In addition, focal necrosis of the cerebellum was seen after adoptive immunization of drug-induced carriers but only when mice received cells at least 3 wk after inoculation, which is probably explained by the gradual spread of infection from membranes to the neural parenchyma during the first month after establishment of the carrier state in adult mice.
Immune spleen cells, when transferred to neonatal carriers, led to a decrease in virus titers in blood and brains and to development of antibody without acute CNS disease.
It appears that the production of fatal choriomeningitis after LCM infection is determined in part by the distribution of viral antigen, and this is markedly different in neonatal and drug-induced carriers at the time of cell transfer. Another factor of potential importance is the much higher level of circulating viral antigen in the plasma of neonatal than in that of drug-induced LCM carriers.
Classical LCM disease can only be transferred by immune lymphoid cells and not by antiserum. Furthermore, little or no complement-fixing (CF) antibody was found in the plasma of mice dying of acute choroiditis. These observations strongly suggest that acute choroiditis is dependent upon the cell-mediated immune response.
CELLS MEDIATING SPECIFIC IN VITRO CYTOTOXICITY
Authors: Golstein Pierre , Wigzell Hans , Blomgren Henric , Svedmyr Erik A. J. 
Published: June 2004

In order to investigate whether only T cells are involved in a cell-mediated cytotoxic system in vitro, we tested the cytotoxicity of immune killing cell populations as deprived as possible of B cells. Educated thymus cells, immune spleen cells purified by filtration through a column of beads coated with antimouse Ig antiserum, and finally educated thymus cells further purified by filtration through such a column fully retained their specific cytotoxic activity. This very strongly suggests that only T cells are involved in the killing of target cells by allogeneic immune cells in vitro, in this system.
Receptor-bearing cells involved in killing in the present system are thus very probably T cells. This point was further strengthened by the demonstration of specific adsorption, on the relevant monolayers, of each of the three above mentioned killing cell populations.
MAGNITUDE AND PATTERN OF THYMIC LYMPHOCYTE MIGRATION IN NEONATAL MICE
Authors: Joel D. D. , Hess M. W. , Cottier H. 
Published: June 2004

Neonatal mice were given a subcapsular, intrathymic injection of thymidine-3H using a modified microneedle technique, and the migration of labeled cells to spleen, lymph nodes, Peyer's patches, and bone marrow was followed radioautographically with time. Assuming that nonlabeled lymphocytes migrated in the same manner as labeled lymphocytes, it can be concluded that the majority of lymphocytes present within mesenteric lymph nodes (74%) and Peyer's patches (61%), and a large proportion of those located in popliteal lymph nodes (40%) and the spleen (26%), were of thymic origin. Evidence is presented indicating that these are minimum values. The difference in the magnitude of thymic cell migration to gut-associated lymphoid tissue on the one hand and to the spleen and popliteal lymph node on the other hand was tentatively attributed to antigenic stimulation from the intestinal flora which develops during the first days of life. Thymus-derived lymphocytes were scattered throughout the lymph node cortex and splenic follicles. No noticeable thymic cell migration to the bone marrow was found. Labeling indices in the peripheral lymphoid organs paralleled those of cortical thymic lymphocytes suggesting the thymic cortex as the major source of migrants.
By 2 days postinjection, the mean grain counts of labeled lymphocytes in all peripheral lymphoid tissues were higher than the mean grain counts of labeled lymphocytes in the thymus. At 7 days postinjection heavily labeled cells constituted 11–16% of the labeled population in peripheral tissues while they were absent from the thymic cortex. These results indicate that a fraction of thymus-derived cells, upon settling in the periphery, remained in, or reentered, a nonproliferative phase for at least 7 days. Conversely, many thymus-derived lymphocytes underwent division in the periphery and/or penetrated the intestinal epithelium.
Since the relative number of thymus-derived cells found in the mesenteric lymph nodes of 1- and 2-day old mice was considerably higher than the percentage of cells at this site having the theta (θ) alloantigen, as reported by other authors, the possibility exists that θ-antigen on thymus-derived lymphocytes may, at least in a fraction of these cells, no longer be detectable as they reach the peripheral organs.
ISOLATION AND PARTIAL CHARACTERIZATION OF LYMPHOCYTE SURFACE IMMUNOGLOBULINS
Authors: Marchalonis John J. , Cone Robert E. , Atwell John L. 
Published: June 2004

Immunoglobulins were isolated from the surfaces of lymphocytes from a variety of lymphocyte populations including murine and human thymus lymphocytes and murine spleen and thoracic duct lymphocytes. Cell surface proteins were labeled with iodide-125I by lactoperoxidase-catalyzed iodination, and recovered in solution either by solubilization in dissociating solvents or active metabolic release. Immunoglobulins were identified and isolated by immunological coprecipitation. The polypeptide chain structure of immunoglobulins isolated from lymphocyte surfaces was analyzed by polyacrylamide gel electrophoresis of reduced, alkylated samples in acid urea. Human and murine thymus lymphocytes possessed only IgM immunoglobulin on their surfaces. This protein contained light chains and µ-type heavy chains and was characterized by a molecular weight of approximately 200,000. Murine splenic lymphocytes from CBA x C57 animals and congenitally athymic (nu/nu) mice possessed both IgM and IgG on their surfaces. The ratio of µ-chain to γ-chain was about 3/1. The presence of IgM on thymus lymphocytes probably does not reflect trace contamination by B lymphocytes because comparable quantities of IgM were isolated from both cell populations. Metabolic turnover data suggest that this immunoglobulin is synthesized by the cell population studied.
These results provide direct evidence for the presence of immunoglobulins composed of light and heavy polypeptide chains on the surfaces of lymphocytes of all classes.
CYTODYNAMICS OF THE IMMUNE RESPONSE IN TWO LINES OF MICE GENETICALLY SELECTED FOR "HIGH" AND "LOW" ANTIBODY SYNTHESIS
Authors: Biozzi G. , Stiffel C. , Mouton D. , Bouthillier Y. , Decreusefond C. 
Published: June 2004

Two lines of mice have been separated by selective breeding for the character "agglutinin production to heterologous erythrocytes." Around the 18th generation of selection the two lines could be considered as homozygous for the character investigated. This trait is under the control of a group of additive genes. The interline difference in the production of anti-SE agglutinins was verified for the range of antigen doses from subimmunogenic to maximal. After intravenous immunization with an optimal dose of SE, the duration of the exponential rise in serum antibody was 4–5 days in both lines. At this time most of the interline difference in responsiveness is already expressed. A cytodynamic study carried out in terms of plaque-forming cells (PFC) and rosette-forming cells (RFC) in the spleen during the exponential phase showed that the principal interline difference is found in the doubling time of cells engaged in the immune response.
More precise cytodynamic analysis made in terms of RFC showed that the doubling time of RFC is 9 hr in high responder and 16 hr in low responder mice. The duration of the exponential rise and the number of target cells stimulated by antigen is the same in both lines. The interline difference at the end of the exponential rise (4 days postimmunization) is larger in terms of serum antibody (30–40-fold) than in terms of PFC or RFC (20- and 11-fold, respectively).
A morphological study of RFC in nonimmunized mice showed that about 90% of rosettes were formed by small lymphocytes in both lines. The remainder were medium-sized lymphocytes. At the peak of the cellular response the RFC have differentiated into large lymphocytes, blast cells, and plasma cells. The contribution of plasma cells to RFC is much greater in the high than in the low line. The cytodynamic and morphologic results presented in this article are compatible with the hypothesis that the group of genes segregated in each line during the selective breeding control and regulate the rate of multiplication and differentiation of the antibody-producing cells.
CONNECTIVE TISSUE SYNTHESIS BY SCLERODERMA SKIN FIBROBLASTS IN CELL CULTURE
Authors: Leroy E. Carwile 
Published: June 2004

Skin fibroblasts from subjects with scleroderma and control subjects were grown in tissue culture to compare the characteristics of connective tissue metabolism. A striking increase in soluble collagen (media hydroxyproline) was observed in eight of nine scleroderma cultures when they were compared with identically handled control cultures matched for the age and sex of the donor and the anatomic site of the donor skin. Glycoprotein content as estimated by hexosamine and sialic acid was also significantly increased in the scleroderma cultures. Estimations of protein-polysaccharide content by uronic acid determinations were low in all cultures and not significantly increased in scleroderma cultures.
This report demonstrates the feasibility of using fibroblast cell cultures to study chronic rheumatic and connective tissue disorders. The initial results suggest a net increase in collagen and glycoprotein synthesis in scleroderma fibroblast cultures. The implications of an abnormality of connective tissue metabolism by skin fibroblasts propagated in vitro in the acquired disorder scleroderma are discussed.
SEPARATION OF STAGES IN THE DEVELOPMENT OF THE "T" CELLS INVOLVED IN CELL-MEDIATED IMMUNITY
Authors: Shortman K. , Brunner K. T. , Cerottini J.-C. 
Published: June 2004

Density distribution analysis in continuous gradients of albumin has been used to study the development of cytotoxic lymphocytes (CL), to separate and characterize the progenitors of CL, and to determine their relationship to subpopulations of T cells.
CL progenitors in the thymus were a homogeneous, medium-density population, distinct from the typical, dense, thymus small-lymphocyte. Activity seemed to be associated with one minor subpopulation of cells with surface antigenic properties characteristic of peripheral T cells (high levels of H-2 antigen, low levels of θ-antigen). CL progenitors in the spleen differed from those in the thymus and normally had the high buoyant density of typical small T lymphocytes. In states of antigenic stimulation, some lighter-density CL progenitors were found in the spleen.
The buoyant density of the CL population developing in the spleens of immunized animals showed progressive changes with time. Early, "immature" CL had the light-density characteristics of large, activated lymphocytes. As the response developed, the density of the CL population increased, and finally approached that of CL progenitors and of typical small lymphocytes.
The data suggest that density subpopulations of T cells represent stages in the development of immunocompetent cells. Possible differentiation pathways of T lymphocytes in the thymus and in the spleen are discussed.
CELL INTERACTIONS IN THE IMMUNE RESPONSE IN VITRO
Authors: Feldmann Marc , Basten Antony 
Published: June 2004

Tissue cultures with two compartments, separated by a cell impermeable nuclepore membrane (1 µ pore size), were used to investigate the mechanism of T-B lymphocyte cooperation. It was found that collaboration was as effective when the T and B lymphocyte populations were separated by the membrane as when they were mixed together. Critical tests were performed to verify that the membranes used were in fact cell impermeable. The specificity of the augmentation of the B cell response by various T cell populations was investigated. Only the response of B cells reactive to determinants on the same molecule as recognized by the T cells was augmented markedly. Specific activation of thymocytes by antigen was necessary for efficient collaboration across the membrane. The response of both unprimed and hapten-primed spleen cells was augmented by the T cell "factor" although, as expected, hapten-primed cells yielded greater responses. The T cell factor acted as efficiently if T cells were present or absent in the lower chamber. Thus the site of action of the T cell factor was not on other T cells, but was either on macrophages or the B cells themselves.
The T cell-specific immunizing factor did not pass through dialysis membranes. The experiments reported here help rule out some of the possible theories of T-B cell collaboration. Clearly T-B cell contact was not necessary for successful cooperation to occur in this system. Possible theoretical interpretations of the results and their bearing on the detailed mechanism of T-B lymphocyte cooperation are discussed.
THE MECHANISM OF ANTIGENIC STIMULATION OF PRIMARY AND SECONDARY CLONAL PRECURSOR CELLS
Authors: Klinman Norman R. 
Published: June 2004

Cell transfers to carrier-immunized irradiated mice have permitted an analysis of the in vitro stimulation of clonal precursors of anti-2,4-dinitrophenyl (DNP) antibody-producing cells derived from both immune and nonimmune mice. The results indicate that: (a) carrier-specific enhancement is obligatory for stimulation of primary precursor cells and increases both the size and number of detectable foci derived from secondary precursors. (b) This carrier-specific enhancement is most apparent in the stimulation of precursors of high-affinity antibody producer cells. (c) The antibody produced by primary foci, like that of secondary foci, appears homogeneous. (d) The frequency of clonal precursors in normal spleens is 38% that in spleens from mice 4–8 months after immunization, and the number of such precursors in normal spleens can be reduced fivefold by specific suppression of donor mice with soluble antigen. (e) The average of association constants of primary monofocal antibodies, like that of primary serum antibody produced in carrier-primed mice, is less than 10-fold lower than that of secondary clonal or serum antibody. (f) The affinity of primary monofocal antibodies shows a slight dependence on stimulating antigen concentration; however, a minimum threshold affinity consonant with stimulation is apparent. (g) Free hapten inhibits antigenic stimulation of primary precursor cells at a much lower concentration than is required for the inhibition of secondary precursors.
These results are interpreted as indicating that (a) primary stimulation, like secondary stimulation, results from the selective stimulation by antigen of a population of cells differing from one another in their potential antibody product but each having only a single such product; (b) the antigen receptors of primary cells interact with antigen as if they are monovalent while receptors of secondary cells evidence multivalence; (c) antigenic stimulation appears to require both a relatively high affinity of receptors for bound antigen and an interlinking of receptors through such antigen; stimulation is thus seen as resulting from a stabilization of receptors within antigen-receptor aggregates to the cell surface; (d) T-cells appear to serve both in cross-linking antigens and in amplifying the size of stimulated clones.
EVIDENCE FOR A BLOOD-THYMUS BARRIER USING ELECTRON-OPAQUE TRACERS
Authors: Raviola Elio , Karnovsky Morris J. 
Published: June 2004

In order to verify the existence of a blood-thymus barrier to circulating macromolecules, the permeability of the vessels of the thymus was analyzed in young adult mice using electron opaque tracers of different molecular dimensions (horseradish peroxidase, cytochrome c, catalase, ferritin, colloidal lanthanum). Results show that although blood-borne macromolecules do penetrate the thymus, their parenchyma] distribution is limited to the medulla of the lobe by several factors: (a) the differential permeability of the various segments of the vascular tree; (b) the spatial segregation of these segments within the lobe; (c) the strategic location of parenchymal macrophages along the vessels.
The cortex is exclusively supplied by capillaries, which have impermeable endothelial junctions. Although a small amount of tracer is transported by plasmalemmal vesicles through the capillary endothelium, this tracer is promptly sequestrated by macrophages stretched out in a continuous row along the cortical capillaries and it does not reach the intercellular clefts between cortical lymphocytes and reticular cells.
The medulla contains all the leaky vessels, namely postcapillary venules and arterioles. Across the walls of the venules, large quantities of all injected tracers escape through the clefts between migrating lymphocytes and endothelial cells; also the arterioles have a small number of endothelial junctions which are permeable to peroxidase, but do not allow passage of tracers of higher molecular weight. The tracers released by the leaky vessels penetrate the intercellular clefts of the medulla, but they never reach the cortical parenchyma, even at long time intervals after the injection.
Therefore, a blood-thymus barrier to circulating macromolecules does exist, but is limited to the cortex. Medullary lymphocytes are freely exposed to blood-borne substances.
IN VITRO ADHERENCE OF SOLUBLE IMMUNE COMPLEXES TO MACROPHAGES
Authors: Arend William P. , Mannik Mart 
Published: June 2004

The adherence of soluble immune complexes to stimulated alveolar macrophages was studied in vitro using HSA-anti-HSA complexes prepared in antigen excess. Those complexes containing more than two molecules of antibody preferentially adhered to macrophages in the absence of complement. Free γG in less than physiological concentrations inhibited the adherence of complexes, and the presence of complement did not significantly alter this inhibition. Complexes prepared with reduced and alkylated antibodies showed a decreased adherence. The strength of binding of soluble complexes to macrophages and their efficiency in fixing complement were greater than seen with small aggregates of homologous γG. These differences in biological properties were observed even though the immune complexes and aggregates contained comparable numbers of γG molecules. The γG receptor on rabbit macrophages exhibited species specificity. Pretreatment of macrophages with proteolytic enzymes led to adherence of larger amounts of soluble complexes.
These observations suggest that the strength of binding of soluble immune complexes to macrophages and their efficiency in fixing complement are not determined solely by a random summation of individual binding sites. It is proposed that conformational changes in the γG antibodies or a specific molecular arrangement in the lattice work of complexes containing large protein antigens may influence the biological properties of the soluble complexes.
THYMUS-DERIVED CELL (T CELL) ACTIVATION BY HETEROLOGOUS ANTIGENS AS A REPLACEMENT OF SPECIFIC IMMUNE T CELLS IN THE TRANSFER OF THE SECONDARY RESPONSE TO SHEEP ERYTHROCYTES
Authors: Mond J. J. , Takahashi T. , Thorbecke G. J. 
Published: June 2004

Spleen cells from LAF1 mice hyperimmune to sheep erythrocytes (SE) lost their ability to transfer a secondary response to irradiated recipients after incubation with anti-θ and rabbit complement in vitro. Small numbers of specific immune cells even when taken 3 days after a primary SE injection reconstituted the direct and indirect plaque-forming cell responses.
Larger numbers of cells sensitized to B. abortus (or keyhole limpet hemocyanin), and given together with the corresponding antigen, also partially reconstituted the ability to respond to SE. This property was mediated by θ-bearing cells and was interpreted as due to a nonspecific humoral factor liberated by specifically activated T cells and acting on B cell proliferation or maturation.