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J L Turk

Publications and source records attributed to J L Turk.

At least 73 records · Page 4Linked to original sources

Major histocompatibility complex class II antigen expression in nerves in leprosy; an immunoelectronmicroscopical study.

A technique for immunoelectronmicroscopy has been used to investigate major histocompatibility class II expression in leprosy nerves. In normal nerves, endothelial cells and occasional endoneural cells (not Schwann cells) were constitutively class II positive. In both paucibacillary and multibacillary leprosy nerve biopsies, infiltrating leukocytes were positive but class II-positive Schwann cells were not seen. These observations indicate that Schwann cells may not be involved in presenting Mycobacterium leprae antigens to T cells in leprosy. This conflicts with evidence from in vitro studies, but may be explained by the fact that in vivo Schwann cells are surrounded by basement membranes and are closely associated with axons.

Antigen-Presenting Cells↗

Differential expression of guinea pig class II major histocompatibility complex antigens on vascular endothelial cells in vitro and in experimental allergic encephalomyelitis.

Previous studies have shown that vascular endothelial cells do not normally express major histocompatibility complex (MHC) Class II antigens either in vivo or in vitro. In this investigation it was found that endothelial in the central nervous system (CNS) of normal guinea pigs constitutively express MHC Class II antigens recognized by the monoclonal antibodies HLA-DR, 27E7, and MSgp8. This phenotype is retained when these CNS-derived endothelial cells are propagated in tissue culture. Furthermore, examination of CNS tissue taken from animals in the acute phase of chronic relapsing experimental allergic encephalomyelitis shows that additional epitopes of the MHC Class II antigen, detected by the monoclonal antibodies CI.13.1 and 22C4, are present during the diseased state. This study not only demonstrates constitutive expression of certain MHC Class II determinants by guinea pig endothelial cells, but also shows that other Class II determinants can be differentially expressed in certain disease states.

Animals↗

Effect of anticancer agents neothramycin, aclacinomycin, FK-565 and FK-156 on the release of interleukin-2 and interleukin-1 in vitro.

Four anticancer agents, neothramycin, aclacinomycin, FK-565 and FK-156, were tested for their effects on concanavalin-A-induced interleukin-2 release from rat splenocytes in vitro. Neothramycin showed an enhancement of the release of interleukin-2, whereas aclacinomycin had no effect. FK-565 and FK-156 were found to inhibit the release of interleukin-2 under similar conditions. The inhibition was much more marked with FK-565. These drugs were also tested for their effects on the release of interleukin-1 from rat peritoneal exudate cells stimulated by lipopolysaccharide in vitro. Neothramycin and aclacinomycin did not affect the release of interleukin-1; however, both FK-565 and FK-156 resulted in its enhanced release under these conditions.

Aclarubicin↗

Effect of anticancer drugs on the release of interferon gamma in vitro.

Some conventional and experimental anti-cancer drugs were tested for their effect on concanavalin-A-induced interferon gamma release from rat splenocytes in vitro. When 2.5 x 10(6) rat splenocytes/ml, stimulated with 1 microgram/ml concanavalin A, were incubated with various non-cytotoxic doses of the vinca alkaloid vincristine, there was an inhibition of the release of interferon gamma in culture supernatants. The antitumour antibiotics bleomycin and Adriamycin, alkylating agents 4-hydroperoxycyclophosphamide and mafosfamide, and the immunoactive peptides FK156 and FK565 did not affect the release of interferon gamma under similar conditions. However, cyclosporin A, in similar experiments, markedly inhibited the release of interferon gamma.

Animals↗

Antigen-specific regulation of T lymphocyte proliferative responses to contact-sensitizing chemicals in the guinea pig.

Skin painting of guinea pigs with either 4-ethoxymethylene-2-phenyloxazol-5-one or 2,4-dinitrofluorobenzene induced not only a primary proliferative response in the draining lymph node but also the systemic suppression of subsequent proliferative responses to topically applied hapten. The inhibition of lymphocyte proliferation, as assessed by the incorporation of [3H]-thymidine and the presence of large pyroninophilic cells in the paracortex, was hapten-specific and long-lasting. This study demonstrates that, in common with the mouse, the sensitization of guinea pigs results in the induction of a hapten-specific suppressor mechanism, which serves to control the proliferative response following reexposure to hapten. However, the antigen-nonspecific suppression of proliferation observed in the mouse following exposure to some potent contact sensitizers was not, under the conditions employed, detectable in the guinea pig.

Allergens↗

The localisation of fibrin, fibronectin and class II major histocompatibility complex antigen in the spinal cord in chronic relapsing experimental allergic encephalomyelitis.

Light and electron immunocytochemistry using antibodies recognising a class II major histocompatibility complex antigen, fibrin, fibronectin, albumin and factor VIII related antigen has been used to stain sections of spinal cord from normal guinea pigs and those with chronic relapsing experimental allergic encephalomyelitis (CREAE). It was found that class II MHC antigens, fibrin and fibronectin were present in normal blood vessels and at high levels in lesions from animals at all stages of the disease. The possible immunological roles of these antigens suggest their participation in the initiation and maintenance of disease state.

Animals↗

An immunoelectronmicroscopical study of the expression of major histocompatibility complex (MHC) class II antigens in guinea pig sciatic nerves following induction of intraneural mycobacterial granulomas.

A guinea pig model of nerve damage in leprosy has been used to investigate the expression of major histocompatibility complex (MHC) class II antigens in granulomatous lesions in nerves. Using an immunoelectronmicroscopical technique, infiltrating mononuclear cells and endoneural fibroblast-like cells are shown to be class II-positive in the experimental neural lesions. Schwann cells are not class II-positive under these conditions, although at the light microscope level Schwann cell-like cells appear to be positively stained. This illustrates the value of immunoelectronmicroscopy in the investigation of cell surface proteins in situ as compared with conventional light immunohistochemistry.

Animals↗

A quantitative immunocytochemical study of the infiltrating lymphocytes in the spinal cord of guinea pigs with chronic relapsing experimental allergic encephalomyelitis.

The production and characterization of an anti-guinea pig B cell monoclonal antibody is described. Immunocytochemical techniques using this antibody and others recognizing a Pan T cell antigen and T cell subsets were employed to study frozen sections of spinal cord from guinea pigs with chronic relapsing experimental allergic encephalomyelitis. T and B cells were found in both perivascular lesions and the central nervous system parenchyma, with the major T cell infiltration occurring by the end of the acute phase of disease. The distribution of T cell subsets suggests a phenotypic selectivity in favour of the transport of CT6 (putative CD8)+ve cells across the blood-brain barrier.

Animals↗

An experimental animal model of granulomatous bowel disease.

A study has been undertaken of the granulomatous response induced in the ascending colon and terminal ileum of the guinea pig by the direct inoculation of mycobacterial antigens. Live BCG (Pasteur) 2 x 10(7) at two weeks induced epithelioid cell granulomas in both large and small bowel and in the draining lymph nodes. The area of infiltration was significantly greater for a given inoculum in the large bowel. Acid fast bacilli were present on Ziehl Neelson stained sections of the large bowel infiltrate, but only rarely in sections from the small bowel lesions. The response to skin testing with a standardised amount of purified protein derivative was less in animals inoculated in the small bowel. Inoculation with 2 x 10(9) cobalt irradiated BCG gave rise, at five weeks, to granulomas containing lesser numbers of epithelioid cells and caseation was sometimes evident. There was a similar but smaller difference in the degree of infiltration at the two inoculation sites. Ziehl Neelson staining failed to reveal the presence of acid fast bacilli in any sections of the bowel infiltrates. Skin testing with purified protein derivative gave a response which was greater in animals inoculated in the small bowel. An identical dose of Cobalt irradiated M leprae induced at five weeks a predominantly macrophage granuloma in both the large and small bowel, with no significant difference in the degree of infiltration at the two sites. No acid fast bacilli were seen in Ziehl Neelson stained sections of the bowel and skin testing with purified protein derivative was reduced. These findings and their relevance to studies of the aetiology of Crohn's disease are discussed.

Animals↗

Regulation of lymphocyte proliferation in contact sensitivity: homeostatic mechanisms and a possible explanation of antigenic competition.

Epicutaneous exposure of mice to the contact sensitizing chemicals 4-ethoxymethylene-2-phenyl-oxazol-5-one (oxazolone) and 2,4,6-trinitrochlorobenzene (picryl chloride) causes an inhibition of proliferative responses induced following subsequent topical challenge. The effects on lymphocyte proliferation comprise both transient antigen non-specific and more persistent hapten-specific mechanisms. Pretreatment of mice with one chemical 5 days prior to sensitization with a second, at which time antigen non-specific influences on proliferative responses are manifest, results in depression of contact sensitization as measured by changes in ear thickness following challenge. If, however, the period between pretreatment and sensitization is extended the inhibition of contact sensitization disappears in parallel with a decline in the antigen non-specific depression of lymph node cell proliferation. These data reveal that there exist two homeostatic mechanisms which control proliferation in response to challenge with at least some antigens, and that the extent of lymphocyte proliferation directly influences the degree of contact sensitization achieved. Moreover these results demonstrate that, in some instances at least, competition between antigens may be a function of immunoregulatory influences on lymphocyte proliferation.

Animals↗

Presentation of myelin basic protein by normal guinea-pig brain endothelial cells and its relevance to experimental allergic encephalomyelitis.

Previous studies have shown that endothelial cells in the central nervous system (CNS) of normal guinea-pigs constitutively express certain MHC class II determinants, whilst the expression of other determinants is apparent during the acute phase of chronic relapsing experimental allergic encephalomyelitis (CREAE). The expression of MHC class II determinants is retained by endothelial cells derived from normal guinea-pig brain tissue and maintained in culture. This present study demonstrates that the MHC class II molecules on these cells can be recognized by allogeneic lymphocytes, resulting in a proliferative response which is enhanced by the addition of exogenous IL-2. The endothelial cells were incapable of presenting either purified protein derivative or ovalbumin, but they could present autologous myelin basic protein (MBP), an encephalitogen implicated in the pathogenesis of EAE. The resulting lymphocyte proliferative response was of the same magnitude as that obtained when a control population of macrophages was used to present MBP. These results, therefore, suggest that cerebrovascular endothelia have the potential to play a role in the pathogenesis of EAE.

Animals↗

An immunoelectron microscopical study of the expression of class II MHC and a T lymphocyte surface marker during chronic relapsing experimental allergic encephalomyelitis.

Immunoelectron microscopy using antibodies recognising Class II MHC antigens and a pan T cell marker was employed to study sections of spinal cord from guinea pigs with chronic relapsing experimental allergic encephalomyelitis (CREAE). It was found that endothelial cells expressed Class II antigens on their luminal surface throughout the course of the disease and that lymphocytes were adherent to these surfaces. In the parenchyma lymphocytes, macrophages and possibly microglia expressed Class II antigens suggesting that they might also be involved in antigen presentation. The different distribution of T cells seen in the individual lesions during the relapse phase may correlate with their respective natural histories.

Animals↗

Phenotypic analysis of guinea pig Langerhans cells with antibodies directed against leucocyte surface antigens.

The epidermis was stained with a panel of recently produced anti-guinea pig leucocyte antibodies. Guinea pig Langerhans cells were not detectable with antibodies directed against B lymphocytes (MSgp9), T lymphocytes (CT7 and MSgp7), T-helper/inducer (MSgp12) and putative T-suppressor/cytotoxic (CT6 and MSgp6) subsets. Langerhans cell expressed both major histocompatibility complex (MHC) class-I and II antigens and also an epitope (CT4) associated with lymphocyte migration, thus suggesting the migratory potential of this cell. Although the Langerhans cell did not express macrophage specific antigens, MSgp5, which detects lymphoid dendritic cells, was weakly expressed on the Langerhans cell. The Langerhans cell expressed a leucocyte-common antigen detected by H201. Double-labelling studies with anti-MHC class-II antibodies indicated that only 0.4 +/- 0.3% of the pan leucocyte-positive epidermal cells were Ia-negative, indicating that it is unlikely that a guinea pig analogue of the murine Thy-1 + dendritic epidermal cell (Thy-1 + dEC) exists.

Animals↗

Behaviour of guinea pig T cells stimulated by antigen, allo-antigen and mitogen.

The expression of major histocompatibility (MHC) antigens on guinea pig T cells was used as a functional marker for lymphocyte activation. Antigen-stimulated lymphocytes were recovered from guinea pigs responding to the contact sensitizer DNFB, and isolated T cells were then phenotyped using a new antiguinea pig monoclonal antibody, MSgp7. The level of expression of MHC class II, as defined by the monclonal antibody, MSgp8, was increased on T cells recovered 4 days after sensitization, as compared with unsensitized controls. The value of this experiment was extended by measuring MHC class II expression on T cells stimulated in vitro by the mitogen concanavalin A, where a clear increase in MSgp8 binding was also observed. Confirmation of the specificity of MSgp8 for guinea pig MHC class II antigens was achieved by studying the inhibitory capacity of this antibody on an MHC class II restricted mixed leucocyte reaction. The combination of antibodies MSgp7 and MSgp8 with flow cytometry could be applied to other guinea pig experimental models to quantitate the expression of MHC class II antigens on T cells to determine their putative value in disease manifestation.

Animals↗

Accessory cell function of dendritic cells from lymph nodes containing Mycobacterium leprae induced granulomas.

Dendritic cells were enriched from guinea pig auricular lymph nodes containing Mycobacterium leprae induced granulomas by immunomagnetic depletion of other cells. These cells were strongly positive for major histocompatibility complex class II antigens and labelled with an antidendritic cell monoclonal antibody, but not with an antimacrophage antibody. Interdigitating dendritic cells were identified in the granulomatous lymph node by staining with the antidendritic cell antibody and by transmission electron microscopy. When cultured in vitro with purified T lymphocytes, these cells acted as accessory cells for both purified protein derivative and concanavalin A induced proliferation. Although previous studies have shown that macrophages from these lymph nodes do not act as accessory cells, the present results indicate that dendritic cells from M. leprae granuloma containing lymph nodes may act as antigen-presenting cells.

Animals↗

AIDS and leprosy.

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Acquired Immunodeficiency Syndrome↗