Thy-1 glycoprotein: structure, distribution, and ontogeny.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
R W Barton
Publications and source records attributed to R W Barton.
A rat model of purine nucleoside phosphorylase deficiency.
Purine nucleoside phosphorylase (NP; EC 2.4.2.1) deficiency is associated with selective T-cell dysfunction and normal B-cell immunity. In order to create an in vivo model of this immune deficiency, we administered 8-aminoguanosine to rats. This water-soluble nucleoside was rapidly converted by NP to the more potent inhibitor 8-aminoguanine, which has a Ki of 0.19 microM. The accumulation of inosine in plasma showed that administration of 8-aminoguanosine was effectively inhibiting NP activity. The administration of 8-aminoguanosine with deoxyguanosine produced increased levels of dGTP only in thymus cells, and increased levels of GTP in cells from thymus, spleen and lymph node and in red cells. This correlated with assays of deoxyguanosine kinase, which showed significantly higher activity in thymus cells than in cells from spleen and lymph node. The intraperitoneal injection of 8-aminoguanosine alone or with deoxyguanosine for 8 consecutive days caused significant decreases in the number of thymus cells (P less than 0.001) and in lymph node and spleen lymphocytes (P less than 0.01). These data showed that the administration of 8-aminoguanosine to rats provided an animal model of NP deficiency that will allow studies of the specific regulation of T-cell function.
Animals↗
The effects of an induced adenosine deaminase deficiency on T-cell differentiation in the rat.
Inherited deficiency of the enzyme adenosine deaminase (ADA) has been found in a significant proportion of patients with severe combined immunodeficiency disease and inherited defect generally characterized by a deficiency of both B and T cells. Two questions are central to understanding the pathophysiology of this disease: (1) at what stage or stages in lymphocyte development are the effects of the enzyme deficiency manifested; (2) what are the biochemical mechanisms responsible for the selective pathogenicity of the lymphoid system. We have examined the stage or stages of rat T-cell development in vivo which are affected by an induced adenosine deaminase deficiency using the ADA inhibitors, erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) and 2'-deoxycoformycin (DCF). In normal rats given daily administration of an ADA inhibitor, cortical thymocytes were markedly depleted; peripheral lymphocytes and pluripotent hemopoietic stem cells (CFU-S) all were relatively unaffected. Since a deficiency of ADA affects lymphocyte development, the regeneration of cortical and medullary thymocytes and their precursors after sublethal irradiation was used as a model of lymphoid development. By Day 5 after irradiation the thymus was reduced to 0.10-0.5% of its normal size; whereas at Days 9 and 14 the thymus was 20-40% and 60-80% regenerated, respectively. When irradiated rats were given daily parenteral injections of the ADA inhibitor plus adenosine or deoxyadenosine, thymus regeneration at Days 9 and 14 was markedly inhibited, whereas the regeneration of thymocyte precursors was essentially unaffected. Thymus regeneration was at least 40-fold lower than in rats given adenosine or deoxyadenosine alone. Virtually identical results were obtained with both ADA inhibitors, EHNA and DCF. The majority of thymocytes present at Day 9 and at Day 14 in inhibitor-treated rats had the characteristics of subcapsular cortical thymocytes which are probably the most ancestral of the thymocytes. Thus, an induced ADA deficiency blocked the proliferation and differentiation of subcapsular cortical thymocytes which are the precursors of cortical and medullary thymocytes.
Adenosine Deaminase↗
Phenotypic heterogeneity of Gross virus-induced thymic lymphomas in the rat: cellular origins and migratory properties.
Neoplastic thymocytes from rat thymic lymphoma-leukemias induced by the rat-adapted Gross leukemia virus (RAGV) were analyzed for a variety of differentiation markers. The neoplasms from individual rats all expressed the antigenic phenotype MP+, W3/13+, Thy-1+, RT-1+, RT-7+, W3/25-. However, approximately two-thirds of the neoplasms were positive for the OX 8 antigen, and one-third were negative. The OX 8- neoplasms only involved the thymus, whereas approximately 40% of the OX 8+ neoplasms involved the spleen as well as the thymus. Virtually all OX 8+ and OX 8- neoplastic cells contained terminal deoxynucleotidyl transferase (TdT), and both OX 8+ and OX 8- lymphomas expressed the lactate dehydrogenase (LDH)-5' isozyme and the primary, but not the secondary, ADA isozyme. This enzymatic phenotype is characteristic of thymocyte precursors, but not thymocytes. Our results therefore indicate that RAGV-induced lymphomas arise from transformed prethymic TdT+ cells which contain the LDH-5' and the primary ADA isozymes. These preleukemic cells presumably migrate to the thymus where they express the RT-7 pan-T-cell antigen and, in some instances, the OX 8 antigen during the development of overt leukemia. The OX 8+ neoplasms, being more differentiated than their OX 8- counterparts, then migrate to peripheral lymphoid tissues.
AKR murine leukemia virus↗
Binding of human lymphocyte-specific monoclonal antibodies to common marmoset lymphoid cells.
Commercially available monoclonal antibodies which bind to human lymphocyte subsets were screened for their ability to bind to lymphoid cells from the common marmoset Callithrix jacchus. Anti-Leu-5 and T11 were the only pan T-cell antibodies which reacted strongly. None of the antibodies which bind human lymphocytes of the helper/inducer subpopulation reacted with C. jacchus cells and only one antibody, T8, specific for the cytotoxic/suppressor subset, bound to the marmoset cells. The two antibodies tested which bind human B cells, B1 and anti-HLA-DR, were also reactive with marmoset cells. The cellular specificity of the T11, T8, and B1 antibodies was determined by dual binding studies on the fluorescence-activated cell sorter. The B1 antibody bound only Ig+ cells and all Ig+ cells were B1+. The T11 and T8 antibodies bound only to Ig- marmoset lymphoid cells and, as in the human, all T8+ marmoset cells were also T11+. Thus, using these monoclonal antibodies in the common marmoset one can identify three populations of lymphoid cells: (1) T11+, T8+ cells; (2) T11+, T8- cells; (3) B1+ cells.
Animals↗
Somatostatin has an antiproliferative effect on concanavalin A-activated rat thymocytes.
Somatostatin, a cyclic tetradecapeptide which is widely distributed in different tissues of the body, exerts an inhibitory effect on numerous cellular processes. It has been observed recently that somatostatin and its analogs were antimitogenic in several established cultured cell lines and in rat tumors. To determine whether this ubiquitous peptide had an antiproliferative effect on a primary culture of rat thymocytes, we observed its effect on the separation of the centrosome (a cell maker of the G1 to S traverse) and DNA synthesis of rat thymocytes activated by concanavalin A. Somatostatin inhibited both indices of proliferation in rat thymocytes at a concentration of 10(-8)M. This observation suggests that somatostatin, which has been localized in the thymus, may play a regulatory role in the growth and development of the cells found in the thymus gland, and may affect thymocyte function in disease states characterized by elevated circulating concentrations of somatostatin.
Animals↗
A comparison of lymphocyte populations in lung tissue and in bronchoalveolar lavage fluid of rats at various times during the development of bleomycin-induced pulmonary fibrosis.
The purpose of this study was to compare lymphocyte populations in lung lavage fluid and in lung tissue during the development of bleomycin-induced pulmonary fibrosis. At various times after bleomycin treatment, animals were killed and lavaged, and lung tissue cells were extracted. Lymphocyte populations were identified by immunofluorescent techniques, using monoclonal antibodies, and quantitated on the fluorescence-activated cell sorter. Normal control rat lung tissue was comprised of 91% T-cells (helper-to-suppressor cell ratio of approximately 1:1) and 9% B-cells. After bleomycin administration, a significant increase in the percentage of B-cells in lung tissue was observed within 3 days, with peak levels (approximately 28%) occurring at 7 days. Changes in the T-cell subset populations were also observed in lung tissue; at 14 days after the administration of bleomycin, the helper-to-suppressor T-cell ratio was 2:1, at 30 and at 120 days, the ratio was reversed to 1:2. These represent significant changes from the 1:1 ratio found in control animals. No lymphocytes were observed in the lavage fluid of control animals or in animals at 30 and 120 days after bleomycin treatment. Significant populations of lymphocytes were found in the lavage fluid at 3, 7, and 14 days after bleomycin treatment. These lymphocytes consisted of approximately 90% T-cells (helper-to-suppressor cell ratio of 1:1) and 10% B-cells. There were no significant changes in the lymphocyte populations found in the lavage fluid after the administration of bleomycin. The results demonstrate that specific lymphocyte populations are changing in lung tissue during the development of the fibrotic process, whereas this shift in populations does not occur in the lymphocyte populations found in lavage fluid.
Animals↗
Anti-idiotypic immunity and autoimmunity. II. Idiotypic determinants of autoantibodies and lymphocytes in spontaneous and experimentally induced autoimmune thyroiditis.
In a previous report, it was demonstrated that heterologous anti-idiotypic antibodies to autoantibodies against rat thyroglobulin (ART) were capable of inhibiting the in vitro binding between ART and rat thyroglobulin. It has also been shown that repeated injections of anti-idiotypic antibodies into Buffalo (BUF) rats with spontaneous autoimmune thyroiditis were followed by a significant decrease in the levels of circulating ART. In this report, cross-reacting idiotypic determinants, detectable by rabbit anti-idiotypic antibodies to ART, are shown to also be present on ART from rats with experimentally induced autoimmune thyroiditis. In addition, antibodies to rat thyroglobulin from animals of various strains and species are shown to also express idiotypes cross-reacting with those of spontaneous ART of BUF rats. Finally, it is reported that idiotypic determinants similar to those of circulating ART are present on spleen lymphocytes from rats with autoimmune thyroiditis.
Animals↗
Expression of adenosine deaminase and purine nucleoside phosphorylase isozymes in lymphohemopoietic precursor cells and normal and neoplastic lymphoid populations.
Explore the source record for details and available documents.
Adenosine Deaminase↗
Identification of thymocyte progenitors in hemopoietic tissues of the rat. II. Enrichment of functional prothymocytes on the fluorescence-activated cell sorter.
A quantitative thymocyte regeneration assay was used to monitor the isolation of functional prothymocytes from rat bone marrow on the FACS. Two prothymocyte subpopulations were tentatively identified on the basis of their relative resistance to dexamethasone. Both populations were comprised of undifferentiated, medium-size cells that displayed large amounts of Thy-1 antigen. Simultaneous sorting of bone marrow cells according to relative low angle light scatter (size) and relative fluorescence intensity for Thy-1 resulted in enrichments of 112-fold and 260-fold, respectively, in prothymocyte activity in untreated and dexamethasone-treated bone marrow. These prothymocyte-enriched cell fractions contained or approximately 75% of total functional prothymocyte activity in bone marrow, and represented 1.1 and 0.35% of total untreated and dexamethasone-treated bone marrow cells. Using these enriched cell fractions, significant thymocyte regeneration is possible with as few as 2 X 10(4) and 1 X 10(4) bone marrow cells, respectively. The possible relationship of these functional prothymocyte subpopulations with CFU-S and with TdT-positive cells is discussed.
Animals↗
The binding of Maclura pomifera lectin to cells of the T-lymphocyte lineage in the rat.
Explore the source record for details and available documents.
Animals↗
Genetic linkage and cell distribution analysis of T cell alloantigens in the rat.
The T cell alloantigens A.R.T.-1, A.R.T.-2, Pta, Ag-F and RT-Ly-2 were examined for linkage to albinism and the haemoglobin variant Hbb, and for cell expression similarities in the rat. The A.R.T.-1 alloantigen was not linked to either A.R.T.-2, albinism or Hbb. The A.R.T.-2 alloantigen was demonstrated to be closely associated to albinism and Hbb with a recombination frequency of approximately 3% with albinism and 1% with Hbb. The four recombinants (out of 104 animals examined) were subsequently analysed with alloantisera to Ag-F, Pta and RT-Ly-2. These alloantisera detected an antigenic system(s) which appeared to co-segregate with A.R.T.-2 in the recombinants studied Characterization of the specific T cell populations expressing each alloantigen demonstrated that removal of the cells bearing any one of the alloantigens removed all the cells expressing any of the other alloantigens. These results demonstrate that the four alloantigenic systems A.R.T.-2, Pta, Ag-F and RT-Ly-2 are located in the same genetic region of linkage group I, and appear to be expressed on the same peripheral T cell subpopulation(s) in the rat.
Animals↗
Differential cellular analysis of bronchoalveolar lavage fluid obtained at various stages during the development of bleomycin-induced pulmonary fibrosis in the rat.
The purpose of this study was to analyze the cellular components of bronchoalveolar lavage fluid throughout the development of bleomycin-induced pulmonary fibrosis in the rat. Animals were killed and lavaged at various times after the administration of a single intratracheal injection of bleomycin. The results demonstrate that a significant influx of inflammatory cells appear in the lavage fluid as early as Day 1 after bleomycin treatment. Polymorphonuclear leukocytes are the first cells to appear and significant concentrations persist for as long as 1 month after bleomycin treatment. There is a very transient yet significant influx of eosinophils on Day 7 after bleomycin treatment. Lymphocytes are present from 3 to 14 days after bleomycin treatment; greater than 97% are T-cells and less than 3% are B-cells. There is a 1:1 ratio of W3/25+ cells (helper cell activity) to OX8+ cells (suppressor cell activity) comprising the lymphocyte population. The blood and lymphoid tissue of these animals contain a normal 2:1 ratio of these subsets. The data demonstrate that specific T-cell populations are present in the air spaces of the lung in response to bleomycin-induced pulmonary fibrosis in this model.
Animals↗
A quantitative assay system for thymocyte regeneration in the rat.
Explore the source record for details and available documents.
Animals↗
Evidence for the cellular origin of Gross virus-induced leukemia in the rat: description of a unique LDH isozyme sub-band in leukemic lymphoid cells and lymphohemopoietic precursor cells.
Neoplastic thymocytes from rat thymic lymphoma-leukemias induced by the rat-adapted Gross-leukemia virus (RAGV) were analyzed for a variety of differentiation markers to define their differentiation state and possible cellular origin. A majority of thymocytes from leukemic rats had the phenotypic characteristics of subcapsular cortical thymocytes that are the most ancestral of the thymocytes. These cells exhibited readily detectable levels of Thy-1 and histocompatibility antigens on their surfaces, they contained terminal deoxynucleotidyl transferase (TdT) and they contained low adenosine deaminase (ADA) and high purine nucleoside phosphorylase (PNP) specific activity. The leukemic thymocytes also contained a sub-band of the LDH-5 isozyme (LDH-5') that was not detected in normal thymocytes but that was present in lymphocyte-rich fractions of postnatal bone marrow, fetal and prepubertal spleen, and fetal and neonatal liver. The tissue distribution and ontogeny of LDH-5'-containing cells is similar to prethymic TdT+ cells in the rat and both TdT and LDH-5' are enriched in a subset of bone marrow "null" cells. These results suggest that TdT+ thymocyte progenitors or their precursors are the targets of leukemic transformation of RAGV.
AKR murine leukemia virus↗
Nucleotide-metabolizing enzymes and lymphocyte differentiation.
Inherited deficiencies of adenosine deaminase and purine nucleoside phosphorylase have been found to be associated with certain immunodeficiency syndromes which are characterized by deficiencies of mature peripheral lymphocytes. The immunodeficiency states associated with these enzyme deficiencies are thought to arise from blocks in lymphocyte differentiation. Deficiencies of these enzymes have profound and apparently selective effects on lymphocyte differentiation. Their discovery has focused attention on previously unknown relationships between purine nucleotide metabolism and lymphocyte development and function. In this article three aspects of nucleotide-metabolizing enzymes and lymphocyte differentiation will be discussed: 1) the distribution of the enzymes among lymphocyte populations at differing stages of differentiation; 2) the possible biochemical mechanisms which give rise to the immunodeficiencies; 3) the stages of lymphocyte differentiation which are affected by the enzyme deficiencies.
Adenosine Deaminase↗
Ontogeny of terminal deoxynucleotidyl transferase-positive cells in lymphohemopoietic tissues of rat and mouse.
The ontogeny of hemopoietic cells which contain the enzyme terminal deoxynucleotidyl transferase (TdT) was studied in rats and mice. During fetal life, TdT-positive cells were first detected in the thymus, where they appeared on or about day 17 of gestation. TdT-positive cells were not found in fetal liver, spleen, or bone marrow, but appeared in bone marrow and spleen on the day after birth. In the rat, peak levels of TdT-positive cells were attained at 3 to 4 weeks of age in thymus, bone marrow, and spleen, accounting for 67, 3.9, and 2.3% of nucleated cells, respectively. The percentages of TdT-positive cells in thymus and bone marrow decreased gradually thereafter, whereas, TdT-positive cells in spleen were no longer detectable by 7 weeks of age. Normal percentages of TdT-positive cells were found in bone marrow and spleen from neonatally thymectomized rats and congenitally athymic (nu/nu) mice. Dexamethasone treatment resulted in a marked decrease in TdT-positive cells. The results are discussed with respect to the putative role of TdT-positive hemopoietic cells as thymocyte progenitors.
Animals↗
5'-Nucleotidase activity in subpopulations of rat lymphocytes.
Rat lymphocyte populations were assessed for 5'-nucleotidase activity by both biochemical and histochemical methods. Enzyme-specific activity was enriched in lymphocyte plasma membrane fractions and was higher in lymph node and spleen lymphocytes than in thymocytes. Histochemical reactions on sections of spleen and lymph node revealed strong activity in the thymus-dependent regions, periarteriolar lymphoid sheath in spleen, and paracortex in lymph node; whereas the thymus-independent regions, follicles, and germinal centers were negative. In cellular depletion experiments, with three different methods to detect 5'-nucleotidase, it was observed that the depletion of T cells, but not B cells, was accompanied by a loss of enzyme activity and a decrease in the percentage of nucleotidase-positive cells. The results suggest that, among members of the lymphocyte series, high 5'-nucleotidase activity is selectively associated with the plasma membranes of peripheral T cells in the rat.
Animals↗