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T W Pearson

Publications and source records attributed to T W Pearson.

87 records · Page 5Linked to original sources

Immune depression in trypanosome-infected mice. II. Characterization of the spleen cell types involved.

Spleen cells from Trypanosoma congolense-infected mice showed a drastic depression in their capacity to respond to B and T lymphocyte mitogens and to allogeneic spleen cells in mixed lymphocyte cultures. Spleen cells from infected mice were also poor stimulators in mixed lymphocyte cultures. The poor responsiveness or stimulation capacity was not due simply to dilution of relevant B or T lymphocytes by the large number of null cells found in the spleens of infected animals. These null cells expressed approximately eight times more H-2 antigen than spleen cells from normal (uninfected) mice and were devoid of Ia antigens.

Animals↗

Immune depression in trypanosome-infected mice. III. suppressor cells.

Spleen cells from trypanosome-infected mice strongly suppressed lymphocyte stimulation induced in normal spleen cell populations by lipopolysaccharide, concanavalin A or allogeneic (H-2-different) stimulator cells. This suppression was not H-2-restricted, as responses of spleen lymphocytes both allogeneic and syngeneic to the suppressors were inhibited. Irradiation or mitomycin C treatment of suppressor populations markedly reduced but did not eliminate suppressor activity. Suppressor populations were effective when present in very low numbers. Addition of suppressor cells to mixed lymphocyte cultures at various intervals after initiation of the cultures showed that the suppressors require 48 h to manifest their activity. Cell depletion or enrichment experiments indicate that the mechanism of suppression is complex and involves more than one cell type.

Animals↗

Suppressor cells in Trypanosoma congolense-infected mice.

Spleen cells from mice infected with T. congolense strongly suppressed lymphocyte stimulation induced in normal spleen cells by incubation with mitogens or allogeneic cells. Cell dilution studies showed that suppressor activity was extremely strong. Suppressor cell activity was markedly reduced by treatment of spleen cell populations with mitomycin-C and was unaffected by treatment with anti-Thy.1 sera and complement. Removal of cells which bound carbonyl iron or which bound to nylon columns, decreased but did not abolish suppressor activity.

Animals↗

The bovine lymphoid system: binding and stimulation of peripheral blood lymphocytes by lectins.

We tested ability of 11 different lectins to stimulate DNA synthesis in bovine peripheral blood lymphocytes, using a wide range of experimental conditions. Five of the 6 lectins which induced DNA synthesis (concanavalin A, succinyl-concanavalin A, phytohemagglutinin M, pokeweed mitogens and lipopolysaccharide) did so under conditions similar to those optimal for stimulation of murine lymphocytes. The other lectin (peanut agglutinin) stimulated normal bovine lymphocytes whereas it does not stimulate normal mouse, rat, guinea pig or human lymphocytes. The binding of 5 different lectins to bovine peripheral blood lymphocytes was measured by fluorescence microscopy. Four of the lectins bound to various proportions of cells. Double labeling experiments using a rhodamine-labeled goat anti-bovine immunoglobulin reagent and fluorescein-labeled lectins showed that both peanut agglutinin and soybean agglutinin bound to lymphocyte populations which were negative for surface immunoglobulin. The majority of lymphocytes negative for surface immunoglobulin bound peanut agglutinin, indicating that this lectin may bind specifically to bovine 'T' lymphocytes.

Animals↗

Immune depression in trypanosome-infected mice. IV. Kinetics of suppression and alleviation by the trypanocidal drug Berenil.

Mice infected with T. congolense were monitored for numbers of parasites in peripheral blood, changes in spleen cell populations, immune depression and suppressor cell activity. Depression of B and T lymphocyte responses and the appearance of suppressor cell activity in spleens of infected mice paralleled the appearance of parasites in the peripheral blood. The immune depression was manifest before any visible changes in spleen cell populations occurred. Treatment of infected mice with the trypanocidal drug Berenil resulted in a rapid clearance of parasites from the peripheral blood, a parallel loss of immune depression and suppressor cell activity and a gradual return towards normal spleen cell composition. The splenic white pulp showed severe depletion following longstanding infection with T. congolense. However, following treatment with Berenil there was rapid repopulation of the white pulp and widespread active germinal centre formation.

Amidines↗

Immune depression in trypanosome-infected mice. I. Depressed T lymphocyte responses.

Using a wide range of experimental conditions, several kinds of T lymphocyte responses in spleen cell populations from trypanosome-infected mice were studied. Lymphocyte stimulation after culture with the mitogen concanavalin A or with histoincompatible cells differing at H-2 or minor lymphocyte-stimulating loci was reduced or abolished in spleen cells from infected mice when compared with responses of spleen cells from uninfected controls. In addition, cytotoxic lymphocytes were not generated in mixed lymphocyte cultures which contained spleen cells from infected animals. Allogeneic skin grafting experiments performed with normal and infected mice showed that a decreased T lymphocyte response also occurs in vivo. The depressed immune responses were not simply due to low numbers of T lymphocytes in spleens of infected animals, but reflected a generalized immune depression which was not antigen-specific.

Animals↗

Calcium transport across avian uterus. III. Comparison of laying and nonlaying birds.

Transepithelial calcium fluxes were measured across isolated uterus of laying, nonlaying, and molting quail under conditions where no electrochemical difference existed across the tissue. Net uterine transfer of calcium in molting and nonlaying birds occurs in the secretory direction and is approximately one-fifth the value obtained for laying birds. The carbonic anhydrase enzyme activity of uteri from laying birds is twice that of uteri from molting birds and five times greater than that of uteri from nonlaying birds. When measured in the presence and absence of 2-mercaptoethanol or dithiothreitol, no statistical difference exists in uterine carbonic anhydrase activities of laying birds or the inhibitory effect of acetazolamide. These results indicate that nonlaying and molting quail secrete calcium at a rate much lower than that of laying quail and that net uterine transfer of calcium exhibits varing degrees of dependence on bicarbonate ion in laying, nonlaying, and molting birds. Carbonic anhydrase data sugges that the activtiy of this enzyme in the quail uterus may be related to uterine calcium secretion.

Acetazolamide↗

Molecular characterization of glycosomal NAD(+)-dependent glycerol 3-phosphate dehydrogenase from Trypanosoma brucei rhodesiense.

The primary structure of a 38-kDa protein isolated from membrane preparations of African trypanosomes was determined by protein and DNA sequencing. Searching of the protein database with the trypanosome translated amino acid sequence identified glycerol 3-phosphate dehydrogenase (EC 1.1.1.8) from various prokaryotic and eukaryotic organisms as the optimal scoring protein. Surprisingly, the eukaryotic trypanosome enzyme showed the highest degree of sequence identity with the corresponding enzyme from the prokaryote Escherichia coli. The trypanosome molecule was expressed in Escherichia coli and found to be enzymatically active, thus confirming the identity of the molecule as an NAD(+)-dependent glycerol 3-phosphate dehydrogenase. A monoclonal antibody specific for the 38-kDa protein was used to localize the enzyme to glycosomes. Immunoblotting showed that the monoclonal antibody bound to a 38-kDa protein in African trypanosomes but not in T. cruzi, Leishmania or Crithidia. The enzyme has a pI of 9.1, a net charge of +17 and contains the peroxisome-like targeting tripeptide SKM at its C-terminus, all characteristic of glycosomal enzymes. Amino acids predicted to be involved in the NAD(+)-dependent glycerol 3-phosphate dehydrogenase active site have diverged from those of the mammalian enzyme. Kinetic analyses of the trypanosome GPD and GPD from rabbit muscle showed that the Km values of the two enzymes are different. The data suggest that the trypanosome protein may be a candidate target for rational drug design.

Amino Acid Sequence↗