摘要:

Two new experimental approaches were established to analyse the influence of the thymus on tolerance induction to major histocompatibility complex (MHC) antigens: The aim of the first experiment was to perform successful transplantation of adult allogeneic thymus tissue into nude mice, an attempt that has been unsuccessful in the past. Tolerance for the MHC genotype of a prospective thymus graft recipient (A) was induced in mice of strain B by injection of (AxB) splenocytes during the neonatal period. Adult thymic tissue obtained from these allogeneic donors (B) were grafted into the nude mice of strain A. The allogeneic thymus was accepted by the nude mice and immunoreconstitution was achieved. Subsequently the recipients developed tolerance to the MHC antigens of the allogeneic thymus donor as proved by mixed lymphocyte cultures and the acceptance of skin grafts. The second experiment was designed to determine which la‐positive thymic compartment participates in confering tolerance to MHC antigens in maturing T lymphocytes. Chimaeric thymus grafts were created by transplantation of neonatal thymus (A) into allogeneic nude mice (B) for a period of 8 weeks. The graft was populated with host bone marrow‐derived la antigen‐positive cells. The chimaeric thymuses consisting of type A epithelium but populated with both type A and B lymphocytes and non‐lymphoid cells (i.e. la‐positive maerophages and dendritic cells), were newly transplanted into nude mice of strain A. The engraftment led to immunological reconstitution and the nude mice acquired tolerance to the MHC antigens expressed by the allogeneic ta‐positive cells populating the chimaeric graft. Irradiation ofthe chimacric thymus prior to transplantation allowed transplantation of chimaeric thymus devoid of living thymocytes but still populated with functionally intact la‐positive non‐lymphoid cells. Transplantation of irradiated chimaeric thymuses resulted in immunoreconstitution and induced exactly the same allotolerance pattern as described above. The results demonstrate that not thymus epithelial cells but a bone‐marow‐derived non‐lymphoid thymus cell, most likely the la‐antigen‐positive thymic macrophage of dendritic cell, is responsible for the induction of tolerance to MHC antigens in

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1987.tb02294.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Mice bearing the ‘auto‐immune’Iprgene develop a lympho‐proliferative disease associated with the production of various antibodies, Lethally irradiated recipients were grafted with bone marrow cells (BMC) from syngeneie mice with or without theIprgene. After 6 months, the survivors were 0/24 and 16/20 for the recipients oflprand normal BMC respectively. The mortality rate was independent of the presence of T lymphocytes among the BMC. Histological evaluation showed that hepatitis, interstitial pneumonitis. and sclerosis of lymphohaemopoietic organs were the major causes of death for the recipients oflprBMC, Hepatitis was associated with an increase in the number of liver interstitial cells (LIC) from about 2x106) up to about 107cells per liver. The LIC associated with the hepatitis were composed of polymorphonuclear leucocytes and large mononuclear leueocytes, showing phenotypic (i.e. Thy. 1−, asialo GM1, presence of cytoplasmic granules) and functional (i.e, non‐phagocytic and cylolytic) properties of NK cells. The disease can be distinguished both from the spontaneous disease of thelprmice (by the absence of‘lprcells'and of anti‐DNA antibodies) and from craft versus host disease hy the absence of cutaneous and intestinal lesions. It may represent a model of tissue injury mediated by large gran

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1987.tb02295.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

The in vitro study of monocytes (Mo) poses several problems. Minor contamination with endotoxin (ET) of media ami utensils as well as adherence to glass or plastic surfaces may activate the cells and cause pronounced production of monokines. Many commercially liquid culture media were found to contain ET in concentrations above 25x10−12g/ml. A simple system for the removal of ET from media and solutions was established by use of a comniercially available Polymyxin B Septiarose gel, To measure the lipopolysaccharide (LFS) binding capacity of the gel. known concentrations of LPS were added to culture media, which were passed through a column consisting or the Polymyxin B Sepharose gel. The content of ET and added LPS in media was measured hy theLimulusamoehocyte lysatc (LAL) test before and after passage of the column. The LPS‐binding capacity of the gel was approximately 2.4 × 10 g/l0 ml. The biological activity of contaminating ET and added LPS in media, before and alter passage of the column, was also characterized by the capacity of the media to induce interleukin l (IL‐1) secretion in human Mo cultures. The content of IL‐l in Mo culture supernalants was determined by the mouse thymocyte costimulatory(LAF) assay. By comparison of the activity of ET in these different biological systems, it was demonstrated that 15‐20 × 10−12g/ml of ET stimulate human Mo cultures lo I

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1987.tb02296.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Human monoeytcs release fibroblast growth‐stimulatory activity. In this study tumour necrosis factor (TNF) has been identified as a major contributor to the monocyte‐derived fibroblast growth‐stimulaiory activity. A neutralizing monoclonal antibody (MoAb) against recombinant TNF (rTNF) inhibited growth of FS‐4 fibroblasts and skin biopsy fibroblasts induced by monocyte supernatants, indicating that TNF was involved in the stimulation. Optimal growth of FS‐4 fibroblasts was induced by monocyte supernatants at dilutions which cointained TNF at a concentration between 1.6 × 10−6and 4.0 × 10−5μg/ml, less growth being induced at higher TNF concentrations. Contrary to this, no optimal concentration interval was found lor rTNF, since increasing rTNF concentrations always resulted in increased growth stimulation. It also appeared that natural TNF in the monocyte supernatants induced growth at a much lower concentration than rTNF tested in the absence of mono

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1987.tb02297.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Human bone marrow, cord blood, and peripheral blood comntain progenitor cells, which during culture mature to histamine‐containing basophilie cells. In bone marrow the histamine content per Alcian blue staining basophilie cell was low before culture. Cultivaiion of BML cells resulted in increased histamine levels in cultures(P<0.05). whereas the basophilic cells did not increase significantly. Cell cultures were stimulated with conditioned medium (CM) produced with allergen‐slimulated cells from atopies and from the Mo T leukaemie cell line. Cells from cultures slimulaled with CM contained less histamine calculated per basophilie cell than did those from unstimulted cultures (P<5.05), There was a significant correlation between the numbers of basophilic cells and the histamine content in cells on day 0 prior to cultivation and after 14 days of cultivation (P<0.01 and P<0.05 respectively). In cord blood there was a correlation between the numhers of basophilie cells and the histamine levels prior to cultivation (P<0.05). During cultivation the number of basophilie cells increased five‐lold (P<0.02), whereas the histamine levels did not inercase resulting in a decreased histamine level per basophilie cell (P<0.02). In peripheral blood the basophilic cells contained the highest levels of histamine. The numbers of hasophilie cells and their conntent of hisiamine showed good correlation both hefore and after unstimtilated and stimulated cultivation (P<0.01). whereas unstimulated cultures did not show such correlation. The results indicate the presence of different proportions of progenitor cells in bone marrow, cord blood. and peripheral blood. all with different ability to produce histamine and become granulated basophilic

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1987.tb02298.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

One hundred and sixty‐five infants were studied longitudinally from birth to 5 years of age. One hundred and twenty‐three school‐age children and 27 adults were examined cross‐sectionally. Total salivary IgA levels and IgA antibodies againstEscherichia coliO antigens were measured. Total IgA levels were low (<20 mg/l) from birth to 4 years of age. At 5 years of age there was a dramatic increase in the total IgA level (geometric mean = 100.7 mg/l), after which the levels fell to values similar to those observed in adults (adult geometric mean = 53.2 mg/l). Low levels of IgA‐specificE. coliantibodies were observed for the first 4 years of life (<1.0 ELISA units). There was a gradual increase in specific antibodies between 5 and 9 years of age (geometric men at 9 years=4.66 ELISA units) to levels similar to those observed in adults (adult geometric mean=8.20 ELISA units). It is suggested that the patterns of development for these variables reflect a balance between antigenic exposure and immune control m

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1987.tb02299.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Purified human peripheral blood T lymphocytes were shown to adhere to growth substrata coated with purified human plasma fibronectin (pFn) and its M1120,000‐140,000 proteolytic fragments containing the cell‐binding site. In contrast, significant binding to laminin‐ or type I collagen‐coated surfaces could not be demonstrated. Binding of T cells to pFn could be inhibited by the synihetic peptidc Arg‐Gly‐Asp‐Ser. Activation of T lymphocytes with concanavalin A (Con A) and a phorbol ester. I2‐O‐tetradecanoyl‐phorbol‐13‐acetate (TPA), led to a higher adherence to pFn than in unstinuilaled, resting T cells. Activation with only Con A in the presence of accessory cells also promoted binding. Increased adherence of T cells to pFn could be demonstrated as early as 2 h after the onset ol stimulation and reached its maximum in 2‐3 days. Furthermore, activated but not resting T cells actively spread on pFn‐coated surfaces and displayed an altered F‐actin organization. In an overlay assay of electrophoretically separated polypeptides of activated T lymphocytes, pFn bound to a high molecular weight polypetide of M, 190,000. suggesting that the cells bind lo pFn via a receptor‐like molecule. Thus, adhesion of pFn may be a two‐stage process. At the first stage cells bind to Fn. Activated T cells proceed to the second stage, where cells begin to spread on pFn. This may be due lo an altered relationship betwee

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1987.tb02300.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

A new monoclonal antibody, MOMA‐2, is described, which recognizes monocytes and macrophages in the mouse. The antibody reacts with the majority of mononuclear phagocytes in various tissues as determined by immunohistochemistry. It differs from other macrophage markers that have been described by the strong reaction with macrophages in the lymphoid organs such as the tingible body macrophages and macrophages in T cell‐dependent areas. The antibody recognizes predominantly a cytoplasmic component, although a membrane component can also be demonstrated. Isolated Langerhans' cells, interdigitating cells and dendritic cells, members of the mononuclear phagocyte system that are involved in antigen presenting, stain weakly with the antibody. Because of the intense staining the antibody is very useful for defining tissue macrophages by immunohistochemis

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1987.tb02301.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

We have previously reported a polymorphism in the mitogenic effect of murine (m) IgG1 anti‐CD3 monoclonal antibodies. This polymorphism was genetically determined and could be attributed to polymorphism of the Fc receptor (FcR) for mIgG1 present on human monocytes. We have now extended these studies by quantitating FcR expression on monocytes and cell lines by a recently developed EA rosette assay, using the erythrocyte‐associated pseudoperoxidase activity. The data show that the polymorphism of the monocyte FcR for mIgG1 is based on a quantitative rather than an absolute difference. Furthermore, this FcR is specific for mIgG1 and does not bind mIgG2a or mIgG2b nor, surprisingly, human IgG. The expression of this FcR on cell lines correlates with their accessory function in IgG1 anti‐CD3‐induced T cell proliferation. mIgG2a can inhibit the rosetting of monocytes with erythrocytes sensitized with human IgG. The FcR detected by this rosette technique can interact with all four human IgG subclasses but not with mIgG1 or mIgG2b. The expression of this type of FcR on human cell lines correlates well with their ability to support mIgG2a anti‐CD3‐induced mitogenesis. These direct measurements of FcR expression support the concept that human monocytes have two independent FcR with affinity for mouse IgG: one receptor specigic for mIgG2a (which also binds human IgG), and a second specifi

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1987.tb02302.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Thirty‐two mycobacterial components were detected by antibodies contained in leprosy patients' sera across the clinical spectrum and rabbit anti‐M. lepraehyperimmune sera by western blot analysis of armadillo‐derivedM. lepraeantigen preparations. Sera of borderline tuberculoid patients were found to contain antibodies recognizing 18M. lepraecomponents. While the reactivity of the sera on the lepromatous pole seemed to be distributed oven the entire molecular weight range, most of the reactivity in the borderline tuberculoid patients was directed at higher molecular weight components (>70,000). Identification of a series of previously unrecognizedM. lepraecomponents offers new possibilities in regard to the potential use of these antigens as targets for immunodiagnosis. Antibodies contained in The rabbit anti‐M. lepraesera reacted with 19M. lepraecomponents. Antigens migrating at 64,000, 38,000, and 22,000 were detected by the rabbit seraonly. Evidence of extensive cross‐reactivity betweenM. lepraeand BCG organisms emphasizes the need to use well‐characterized antibody probes to determine the specificity of select mycobacterial antigens. The potential usefulness of rabbit monospecific hyperimmune sera to selectM. lepraefractions in immunodiagnosis, in immune regulation studies, or as a tool to screen for mycobacterial products in lambda gt11 phage lysates ofE. coliis discussed. SelectM. lepraecomponents were partially purified and their recovery assessed through SDS‐PAGE analysis of Coomassie blue

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1987.tb02303.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY