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M Dohlsten

Publications and source records attributed to M Dohlsten.

143 records · Page 8Linked to original sources
PubMed1988

Lymphocyte subpopulations and lymphokine production in children with constitutional aplastic anemia.

The expression of lymphocyte surface markers as well as the production of interleukin-2 (IL-2) and interferon-gamma (IFN) by mitogen-stimulated peripheral blood mononuclear cells (MNC) have been studied in five children with constitutional aplastic anemia. A significantly reduced T4/T8 ratio was found and two of five patients also had a reduced percentage of B cells. One patient had a high percentage of HLA-DR positive T8+ cells, very suggestive of a high degree of circulating activated T suppressor/cytotoxic cells. IL-2 production was reduced in two patients, whereas IFN production was only reduced in one of these. The abnormalities found correlate with the duration of the bone marrow failure. The patients with the longest duration of bone marrow failure also exhibited the lowest T4/T8 ratio. No spontaneous IFN production was detected in any of the patients. There was no clinical benefit or reversal of the immune abnormalities during and following treatment with cimetidine and cyclosporine A in two patients.

Anemia, Aplastic↗
PubMed1987

Histamine acts directly on human T cells to inhibit interleukin-2 and interferon-gamma production.

Histamine acts directly on human T cells to inhibit lymphokine production without the involvement of accessory cells. Histamine inhibits the production of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) by purified human peripheral T cells activated in the presence of either intact monocytes or metabolically inactive fixed Raji and U698 cells as accessory cells. Purified T cells do not respond more than marginally to staphylococcal enterotoxin A (SEA) or phytohemagglutinin (PHA) in the absence of accessory cells. However, activation by the phorbol ester PMA in conjunction with either PHA or the calcium ionophore A23187 induces large amounts of IFN-gamma and IL-2. Histamine suppresses the lymphokine production in these pure T-cell cultures to a similar extent as in monocyte-containing cultures. Histamine is also shown to suppress DNA synthesis by purified T cells cultivated at a low cell density, eliminating any possible involvement of small numbers of contaminating accessory cells. In vitro preactivated T cells are shown to retain their capacity to respond to histamine when stimulated by PMA and A23187 or by mitogen in the presence of Raji cells. The conclusion that histamine acts directly on T cells and does not require accessory cells to induce suppression is further confirmed by the demonstration that IL-2 production by the human T-cell leukemia line Jurkat was significantly suppressed by histamine in a H-2 receptor-restricted manner.

Antigen-Presenting Cells↗
PubMed1987

Catalase and lipopolysaccharide enhance proliferation in the rat mixed lymphocyte reaction.

Proliferation of rat spleen cells in a mixed lymphocyte culture was amplified fivefold or more in the presence of 2000 units of catalase/ml, as measured by [3H]thymidine incorporation. A similar effect was observed with 1 microgram of lipopolysaccharide (LPS)/ml. Addition of polymyxin B abrogated the promotional effect of LPS, but not that of catalase. These results indicate that the hydrogen peroxide generated by some cells in the rat spleen cell mixed lymphocyte culture suppresses the proliferative response. The demonstration that removal of plastic adherent cells (reducing the percentage of monocytes/macrophages by 75-80%) also results in a 5- to 10-fold increase in a subsequent MLR, indicates that some of the adherent cells may be the producers of hydrogen peroxide, which at higher concentrations suppresses the T-cell proliferation. The enhanced proliferation was not mainly due to increased interleukin 2 (IL-2) production, since the IL-2 concentrations of catalase and LPS-containing cultures were lower than those of control cultures.

Animals↗
PubMed1987

Binding of histamine-albumin conjugates to human lymphocytes: evidence for labelling of histamine H-1 but not H-2 receptors.

Histamine conjugated to human serum albumin (HSA) bound to a major proportion of human peripheral blood lymphocytes in a rosetting assay. In contrast, red cells coated with the control conjugates pentylamine-HSA and ethanolamine-HSA were unreactive. Amine conjugation by the carbodiimide method imposed a positive charge on the albumin molecule. However, the percentage histamine-HSA-binding lymphocytes was related to the amount of histamine coupled to the albumin molecule and not to differences in isoelectric point (pI) of the modified protein carriers. Four different histamine-albumin conjugates and one pentylamine-HSA conjugate inhibited lymphocyte binding of histamine-HSA, whereas ethanolamine-albumin, carbodiimide-reacted HSA and native albumin were not inhibitory. The histamine H-2 receptor antagonists cimetidine, ranitidine, metiamide, and burimamide lacked inhibitory effects. The histamine H-1 receptor antagonists clemastine, mepyramine, and diphenhydramine efficiently inhibited lymphocyte binding of the histamine-albumin conjugate with IC50 values of 0.2, 1, and 40 mM, respectively, indicating interactions with low affinity H-1 receptors.

Binding, Competitive↗
PubMed1986

Histamine in endocrine cells in the stomach. A survey of several species using a panel of histamine antibodies.

Antibodies to histamine were used to examine the localization of the amine in cells of the stomach and upper small intestine of a great variety of species, including cartilaginous and bony fish, amphibia, reptiles (lizard), birds (chicken) and a large number of mammals. In all species gastric histamine was localized in endocrine cells (invariably found in the epithelium) and mast cells (usually with an extra-epithelial localization). The endocrine cells were identified as such by immunostaining with antibodies to chromogranin A and the mast cells were identified by toluidine blue staining. Histamine-immunoreactive endocrine cells were found almost exclusively in the acid-producing part of the stomach; only rarely were such cells observed in the pyloric gland area. They were fairly numerous in the gastric mucosa of the two subclasses of fish as well as in the amphibia and reptile species studied. Here, the majority of the histamine-immunoreactive endocrine cells seemed to have contact with the gastric lumen (open type cells) and were located in the surface epithelium (certain fish only) or together with mucous neck cells at the bottom of the pits. In the chicken, histamine-immunoreactive endocrine cells were numerous and located peripherally in the deep compound glands. They were without contact with the lumen (closed type) and had long basal extensions ("paracrine" appearance), running close to the base of the oxyntic-peptic cells. In mammals, the number of histamine-immunoreactive endocrine cells in the stomach varied greatly. They were particularly numerous in the rat and notably few in the dog, monkey and man. In all mammals, the histamine-immunoreactive endocrine cells were of the closed type and located basally in the oxyntic glands. They often had a "paracrine" appearance with long basal processes. Histamine-storing mast cells, finally, were few in both subclasses of fish as well as in the amphibian species and in the lizard. They were fairly numerous in chicken proventriculus (beneath the surface epithelium), few in the oxyntic mucosa of mouse, rat and hamster, moderate in number in hedgehog, guinea-pig, rabbit, pig and monkey, and numerous in cat, dog and man.(ABSTRACT TRUNCATED AT 400 WORDS)

APUD Cells↗
PubMed1986

Histamine inhibits interferon-gamma production via suppression of interleukin 2 synthesis.

Histamine, a modulator of various immune functions, inhibits the production of interleukin 2 (IL-2) and interferon-gamma (IFN-gamma) by polyclonally activated human blood mononuclear cells. The histamine-induced inhibition of IFN-gamma synthesis can be completely eliminated by the addition of recombinant IL-2. The IFN-gamma synthesis by T8+ lymphocytes is highly dependent on IL-2 supplied either by the IL-2 producing T4+ lymphocytes or through exogenous addition of recombinant IL-2. It is concluded that histamine acts primarily on the interleukin 2 synthesis by the T4+ lymphocytes and as a consequence of this inhibition, interferon-gamma production is reduced.

Histamine↗
PubMed1986

Production and characterization of rabbit antibodies against histamine.

Antisera were raised in rabbits against histamine conjugated to human serum albumin (HSA) by the carbodiimide (ECDI) method. The specificity of the antisera was studied in a radioimmunoassay using 125I-protein A for detection of IgG binding. The HIS-HSA antisera reacted with histamine-HSA conjugates prepared by either the carbodiimide or diisocyanate coupling procedure, as well as with carbodiimide-prepared histamine-ferritin and histamine-ovalbumin conjugates. On the contrary, the antisera were unreactive with unconjugated HSA, ECDI-reacted HSA, or HSA conjugated to ethanolamine or pentylamine. Free unconjugated histamine significantly inhibited antibody binding to histamine-HSA and 50% inhibition of antibody binding (IC50) was recorded at 3 mM histamine concn. On a histamine molar concn basis a much lower inhibitory potency of free histamine was recorded, as compared to histamine-protein conjugates (IC50 = 3 X 10(-6) mM). This probably reflected amplification of antibody binding to the multivalent ligand, but possibly also that the protein carrier adds some common features to the antigenic determinant. Histidine, ornithine, glutamine, asparagine, sterylamine and several other amino acids lacked inhibitory effects. Histamine H1 and H2 receptor antagonists inhibited histamine binding to the histamine antibodies. The antagonists varied in their affinity for the histamine antibodies and 50% inhibition of antibody binding was recorded in the range of 1-50 mM concn of the antagonists. Comparing one H1 and one H2 antagonist (diphenhydramine and cimetidine, respectively) two of the sera were preferentially inhibited by cimetidine whereas the third serum seemed to be more prone to inhibition by diphenhydramine.

Animals↗
PubMed1986

Synergistic action of gamma interferon and catalase to reverse the suppressive effect of peritoneal macrophages on concanavalin A-induced lymphocyte proliferation.

The suppressive effect of normal rat peritoneal exudate cells (PEC) on concanavalin A (Con-A)-induced lymphocyte proliferation was studied. Partial suppression of proliferation was obtained by adding 3% PEC and complete suppression was observed with 6% PEC. The suppressive effect was mediated by W3/25+ plastic-adherent macrophages, which constitute about 60% of normal PEC. Addition of PEC prior to, simultaneously with, or 24 h after, but not 48 h after, the stimulation of lymphocytes with Con A resulted in suppression. Suppressed cultures produced normal or slightly increased amounts of interleukin 2 (IL-2), but the expression of the IL-2 receptor on lymphocytes was decreased. Pre-exposure of PEC to gamma interferon (IFN-gamma) resulted in decreased suppression, whereas IFN-gamma added simultaneously with the lymphocytes had no effect. Catalase reversed PEC-induced suppression and significant synergistic effects were recorded when combined with IFN-gamma. Even completely suppressed cultures were effectively protected from suppression. Indomethacin and combinations of indomethacin with catalase or IFN-gamma did not result in additional protection from PEC-mediated suppression.

Animals↗
PubMed1986

Effect of cyclophosphamide pretreatment on autoimmune encephalomyelitis in rats.

We studied the effect of a low dose cyclophosphamide (CY) treatment on the clinical course of experimental autoimmune encephalomyelitis (EAE) in rats from three resistant or low-susceptible strains: Fischer, Brown-Norway, PVG, and the F1 hybrid between the two former strains. Treatment with 40 mg/kg two days before immunization resulted in a marked potentiation of EAE development in Fischer and PVG rats, but not in BN rats or F1(BN X F) hybrids. The effect of the CY treatment was a short period of severe lymphoid cell depletion with an increase in the quotient between T cells reacting with w3/25 monoclonal antiserum and such reacting with ox-8 antiserum, indicating a relative reduction in suppressor/cytotoxic cell counts. Treatment of Fischer or PVG rats, after CY treatment, for five days with thymic hormone factor (THF) normalized T cell ratios and restored the rats to a state of low susceptibility. It is concluded that Fischer and PVG rats have an EAE suppressive mechanism dependent on CY-sensitive suppressor lymphocytes, while there may be other mechanisms of resistance to EAE in BN rats.

Animals↗
PubMed1986

Immunological abnormalities in a child with constitutional aplastic anemia.

This case report describes a child with severe constitutional hypoplastic anemia and Seckel's syndrome. Immunological analysis on mononuclear peripheral blood cells revealed an abnormally low ratio of T-helper to T-suppressor/cytotoxic cells and a highly increased number of HLA-DR-positive T suppressor/cytotoxic cells. Interferon-gamma and interleukin-2 production by mitogen-stimulated peripheral blood mononuclear cells was slightly reduced, and no spontaneous production of these lymphokines was seen. The immunological abnormalities demonstrated in this case of constitutional aplastic anemia may indicate common features with acquired aplastic anemia.

Abnormalities, Multiple↗
PubMed1985

Histamine modulates the production of interferon-gamma and interleukin-2 by mitogen-activated human mononuclear blood cells.

Histamine inhibited the production of interferon-gamma and interleukin 2 (IL-2) induced in human peripheral blood mononuclear cells by Staphylococcal Enterotoxin A (SEA) but had no effect on the expression of IL-2 receptors. The effects on lymphokine production were dose dependent with maximal inhibition occurring at histamine concentrations of 10(-4) to 10(-6) M. The H2-agonist 4-methylhistamine but not the H1-agonist 2-methylhistamine modulated lymphokine production in a similar manner as histamine. Histamine at concentrations of 10(-3) to 10(-8) M had no inhibitory effect directly on the activity of admixed IL-2 containing medium. The inhibitory effects of histamine could be reversed by the H2-antagonist cimetidine but not by the H1-antagonist diphenhydramine. This indicates that the inhibitory effects of histamine on lymphokine production are mediated through H2-receptors on mononuclear cells.

Dose-Response Relationship, Immunologic↗
PubMed1985

Immunological studies in a patient with the glucagonoma syndrome.

The glucagonoma syndrome is a rare clinical entity characterized by a glucagon-producing tumor of the pancreas, necrolytic migratory erythema, weight loss and usually decreased glucose tolerance. Lately there has been increasing interest in the interaction of peptide hormones and the immune system, implicating a regulatory role of the peptide hormones on immune activation and function. We present a patient with metastasizing glucagonoma and highly elevated plasma levels of glucagon and pancreatic polypeptide. Normal numbers of peripheral blood lymphocytes with normal proportions of the T and B populations were seen. Within the T lymphocyte population the percentage of T4+ cells (helper phenotype) was increased with a concomitant decrease in T8+ cells (suppressor/cytotoxic phenotype), resulting in an abnormally high T4/T8 ratio of 6.7 (mean reference value 1.8). Functional tests demonstrated a normal tuberculin reaction and adequate lymphocyte responses in vitro to polyclonal activators. Furthermore we noticed a urine electrophoretic pattern consistent with a proximal tubular kidney defect. It is concluded that studying the immune system in patients with endocrine active pancreatic tumors may give clues on the influence of pancreatic peptide hormones on immune function and regulation.

Adenoma, Islet Cell↗
PubMed1984

Staphylococcal protein A (SpA) does not induce production of interferon-gamma in human mononuclear blood cells.

Preparations of protein A (SpA) from Staphylococcus aureus and low-molecular-weight SpA induce production of interferon-gamma (IFN-gamma) and are potent mitogens when added to human lymphocytes. The IFN-gamma-inducing and main mitogenic activity of these preparations can be separated from SpA by gel filtration and affinity chromatography. These activities can also be partially inhibited by antiserum to staphylococcal enterotoxin A (SEA) in a specific manner. It is concluded that the IFN-gamma-inducing activity and most of the mitogenic activity of SpA preparations are not attributable to intact or low-molecular-weight fragments of SpA but depend on the presence of SEA and other non-SpA products in the preparations of SpA.

Chromatography↗
PubMed1984

Demonstration of histamine receptors on human platelets by flow cytometry.

Fluoresceinated human albumin conjugated with histamine (FHA-HIS) has been used for the demonstration of histamine receptors on human platelets. Such receptors were demonstrated on 40-63% of peripheral blood platelets in 4 healthy donors. The binding of FHA-HIS was inhibited on 35-79% of the platelets by the histamine H1 receptor antagonists diphenhydramine and clemastine. The histamine H2 receptor antagonist cimetidine blocked the FHA-HIS binding on 14-37% of the platelets. It is concluded that histamine H1 as well as H2 receptors occur on human platelets but the receptors are not equally distributed in the platelet population.

Blood Platelets↗
PubMedDate not supplied

Targeting of superantigens.

The bacterial superantigen staphylococcal enterotoxin A (SEA) is an extremely potent activator of T lymphocytes when presented on MHC class II antigens. In order to induce T lymphocytes to reject a tumor, we substituted the specificity of SEA for MHC class II molecules with specificity for tumor cells by combining SEA with a MAb recognizing colon carcinomas. Chemical conjugates or recombinant fusion proteins of the MAb C215 and SEA retained excellent antigen binding properties whereas the binding to MHC class II was markedly reduced. The hybrid proteins directed SEA responsive T cells to tumors with specificity determined by the specificity of the MAb. Significant tumor cell killing was obtained at picomolar concentrations of the hybrid proteins and was the result of direct cell mediated by cytotoxicity as well as production of tumoricidal cytokines by T cells. Targeting of superantigens represents a novel approach to specific immunomodulation and deserves further study as a potential therapy for malignant disease.

Antibodies, Monoclonal↗
PubMedDate not supplied

Preparation and characterization of conjugates of monoclonal antibodies and staphylococcal enterotoxin A using a new hydrophilic cross-linker.

Conjugates between monoclonal antibodies recognizing human cancer cells and the superantigen staphylococcal enterotoxin A (mAb-SEA) represent a potential novel approach to tumor therapy. Such mAb-SEA conjugates direct T-cells to lyse colon carcinoma cells in vitro. The synthesis of mAb-SEA conjugates which were prepared by introducing thiol groups on SEA and iodoacetyl or maleimide groups on mAb forming a stable thioether linkage between SEA and mAb is described. A hydrophilic spacer, composed of repeated ethylene oxide units, was constructed to increase the distance between SEA and mAb, preserving biological activity of both proteins. The degree of modification of mAb with SEA was determined with SDS-PAGE. Variables influencing the composition of the conjugates and their effect on the tumor-cell cytotoxicity were studied and optimal conditions for the synthesis were established. Functionally active mAb-SEA conjugates were prepared from a panel of different mAb and T-cell-dependent cytotoxicity against several human cancer types including colon, ovarial, breast, and renal cancer was obtained. This suggests that mAb-SEA conjugates may be of value in the treatment of human neoplastic disease.

Antibodies, Monoclonal↗