Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.5.4.4 (adenosine deaminase)
 5,136 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Evidence of an acquired T cell-specific deficiency distinct from acquired immunodeficiency syndrome (AIDS) in a 63-yr-old Japanese female is provided. Recently, this patients suffered from primary invasive pulmonary aspergillosis. Skin tests to purified protein derivative of tuberculin (PPD) and Aspergillus antigens were negative. Upon admission to our hospital, her lymphocytes were exclusively unresponsive to T cell mitogens (concanavalin A, phytohemagglutinin, and OKT 3). The level of cells defined by monoclonal antibodies (CD1, CD2, CD3, CD4, WT31, and CD5) was less than 3%. In contrast, no decrease in the number of red blood cells, platelets, neutrophils or B cells was apparent. Five years ago, the patient had a normal white blood cell and lymphocyte count. However, over the following 4 yr, she developed lymphopenia. With medication, her pulmonary disease recovered, while lymphopenia still continued. The levels of immunoglobulins, complements and enzyme activities (adenosine deaminase and purine nucleoside phosphorylase) were normal. Moreover, several tests for HIV (ELISA and Western bolt) were negative suggesting that the T cell-specific deficiency was not a congenital immunodeficiency or AIDS but rather a new type of acquired immunodeficiency.
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PMID:Acquired T cell specific deficiency other than acquired immunodeficiency syndrome (AIDS). 156 29

We have previously shown that stimulation of the Ti/CD3 receptor complex on human T-cells potentiates adenylate cyclase activation by adenosine or forskolin. Anti-CD2 receptor antibodies shared with anti-CD3 antibodies the ability to potentiate dose dependently the adenosine- and forskolin-stimulated cyclic adenosine monophosphate (cAMP) accumulation, whereas stimulation of the CD45 receptor had no effect on cyclase activity. Modulation of the CD3 complex with anti-CD3 antibodies was found to decrease the CD2 receptor effect on adenylate cyclase activity greatly. The possible involvement of CD3-stimulated phospholipase C (PLC) activation on the cAMP potentiation was examined using HPB-ALL cells that express a CD3 complex with a defect coupling to PLC. Stimulation of the CD3 complex on HPB-ALL cells had only slight effects on adenosine-stimulated cAMP formation, whereas the effect on forskolin-stimulated cAMP was virtually unchanged. The CD3 effect was further analyzed in Jurkat cell membranes. In contrast to the results obtained after stimulation of intact cells, it was found that OKT3 stimulation of membranes did not potentiate the forskolin response. Finally, we tested whether inhibition of endogenous adenylate cyclase agonist production affected the CD3 effect. Inhibition of adenosine production or adenosine breakdown with 8-p-sulphophenyl theophylline (8-PST) or adenosine deaminase (ADA), respectively, did not alter the CD3 effects. Indometacin, which inhibits prostaglandin production, also had no effect. Together, these data show that stimulation of the CD2 receptor potentiates adenylate cyclase responses by a mechanism that is dependent on CD3 expression. Furthermore, the CD3 effect on cAMP appears to be mediated by two different mechanisms, one which is, and one which is not dependent on PLC. Finally, this effect is not due to an endogenous production of adenylate cyclase agonists.
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PMID:CD3-dependent increase in cyclic AMP in human T-cells following stimulation of the CD2 receptor. 167 13

Adenosine deaminase (ADA) expression on the surface of mitogen-stimulated lymphocytes was studied by flow cytometry. The gate for lymphocytes was located by cell size (forward scatter), cytoplasmic complexity (side scatter) and by expression of the markers CD2, CD4, CD8 and CD19. After mitogenic proliferation two populations appeared, one corresponding to non-stimulated cells, and the other consisting of larger cells which showed relatively high expression of adenosine deaminase on their surface. The increase was similar to that observed for CD71 expression, and paralleled the increase in 3H-thymidine incorporation. There was a correlation between ADA and CD71 expression (r = 0.92 for phytohaemagglutinin (PHA) and 0.97 for pokeweed mitogen (PWM)). These results suggest a role for ecto-adenosine deaminase in lymphocyte proliferation and/or triggering.
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PMID:Surface expression of adenosine deaminase in mitogen-stimulated lymphocytes. 834 57

Peripheral blood, bone marrow and/or lymph nodes of 77 patients with T- and B-ALLs/lymphomas were characterized for their surface membrane marker profiles using flow cytometry and fluorescence microscopy. Purine metabolism enzyme activities were compared with membrane immunophenotypes. T and B-ALLs/lymphomas subtypes were defined by the expression of surface membrane antigens detected by the monoclonal antibodies. Based on immunophenotyping we found the following characteristic marker profiles: in T-ALL-CD7, CD2, CD1, CD5, CD3, CD4, CD8, CD38, CD71; in T-NHL-CD7,CD2,CD3,CD4,CD5,CD6; in pre-B ALL-CD10, CD19, CD24, HLA-DR, CD34, in B-ALL-CD19, CD20, CD24, HLA-DR, SmIg with kappa or lamda light chains; in B-ALL-weak SmIg, kappa or lambda, CD19, CD20, CD24, CD5, HLA-DR; in B-NHL-CD19, CD20, CD22, CD24, CD5, more intensive SmIg, kappa or lambda. The cells of leukemic cases tended to have more immature phenotypes than those of lymphoma cases. Analysis of purine metabolism enzyme activities showed that there was a correlation between the values of adenosine deaminase (ADA) and purine nucleoside (PNP) and various types of T- and B-ALLs/lymphomas. ADA levels in B-NHL and B-CLL were lower than those in normal cells, while ADA level in T-ALL, T-NHL, pre-B-ALL and B-ALL was higher (the average 185,92,73,63 pkat. 10(-6)cells, respectively). ADA activity was significantly different between lymphocytes of control group and T-ALL(p<0.01), between T-ALL and T-NHL(p<0.05), between T-NHL and B-NHL(p<0.05) and between T-ALL and B-NHL(p<0.05). PNP activities were lower to those in normal cells. ADA/PNP ratio increased mostly in T-ALL, less in T-NHL, pre-B-ALL and B-ALL (10.8 and 5.3 and 2.2, and 2.0 respectively). ADA/PNP ratio was significantly different between T-ALL and pre-B-ALL(p<0.05) and between T-ALL and B-NHL(p<0.05).
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PMID:A comparison of some leucocyte differentiation markers and the adenosine deaminase and purine nucleoside phosphorylase values in B and T cell leukemias and lymphomas. 859 72

We introduced the locus control region (LCR) of the human CD2 gene in eight different ways into retroviral constructs containing the human adenosine deaminase (hADA) gene. Two of these constructs were tested in transgenic mice. Neither expressed hADA in any examined tissue, nor did control vectors without the LCR insert. Amphotropic retrovirus vector producer cell clones were isolated and analyzed for provirus integrity and vector titer. Three constructs yielded recombined proviruses in 20-100% of transduced clones, whereas the other five constructs always rendered viruses that remained stable upon replication and gave vector titers comparable to the control lacking an LCR. Human ADA-deficient T cells and murine fibroblasts transduced with these recombinant viruses showed considerable hADA expression levels that were, however, not significantly different from those of cells transduced with the control vector lacking an LCR insert. Furthermore, no difference in hADA expression levels could be detected in spleen, thymus and bone marrow of long-term repopulated mice that had received bone marrow cells transduced with either the control vector or one of two different CD2-LCR containing vectors. In conclusion, the CD2-LCR does not alleviate the expression block for recombinant retroviruses in the germ line and does not enhance the LTR-driven expression in T cells.
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PMID:Expression pattern of CD2 locus control region containing retroviral vectors in hemopoietic cells in vitro and in vivo. 961 51

CD26 has proved interesting in the fields of immunology, endocrinology, cancer biology and nutrition owing to its ubiquitous and unusual enzyme activity. This dipeptidyl aminopeptidase (DPP IV) activity generally inactivates but sometimes alters or enhances the biological activities of its peptide substrates, which include several chemokines. CD26 costimulates both the CD3 and the CD2 dependent T-cell activation and tyrosine phosphorylation of TCR/CD3 signal transduction pathway proteins. CD26 in vivo has integral membrane protein and soluble forms. Soluble CD26 is at significant levels in serum, these levels alter in many diseases and soluble CD26 can modulate in vitro T-cell proliferation. CD26, being an adenosine deaminase binding protein (ADAbp), functions as a receptor for ADA on lymphocytes. The focus of this review is the structure and function of CD26 and the influence of its ligand binding activity on T-cell proliferation and the T cell costimulatory activity of CD26.
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PMID:CD26: a multifunctional integral membrane and secreted protein of activated lymphocytes. 1155 88

Adenosine is an immunosuppressive molecule that is associated with the microenvironment of solid tumors. Mouse T cells activated with anti-CD3 antibody in the presence of adenosine with or without coformycin (to prevent adenosine breakdown by adenosine deaminase) exhibited decreased tyrosine phosphorylation of some intracellular proteins and were inhibited in their ability to proliferate and synthesize interleukin (IL)-2. In addition, adenosine interfered with activation-induced expression of the co-stimulatory molecules CD2 and CD28. Activation-induced CD2 and CD28 expression was also diminished when T cells were activated in the presence of anti-IL-2 and anti-CD25 antibodies to neutralize IL-2 bioactivity. Collectively, these data suggest that CD2 and CD28 up-regulation following T cell activation is IL-2-dependent; and that adenosine inhibits activation-induced T cell expression of CD2 and CD28 by interfering with IL-2-dependent signaling. The inhibitory effect of adenosine on activation-induced CD2 and CD28 expression could not be attributed to cyclic AMP (cAMP) accumulation resulting from the stimulation of adenylyl cyclase-coupled adenosine receptors, even though cAMP at concentrations much higher than those generated following adenosine stimulation was inhibitory for both CD2 and CD28 expression. We conclude that adenosine interferes with IL-2-dependent T cell expression of co-stimulatory molecules via a mechanism that does not involve the accumulation of intracellular cAMP.
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PMID:Adenosine inhibits activation-induced T cell expression of CD2 and CD28 co-stimulatory molecules: role of interleukin-2 and cyclic AMP signaling pathways. 1287 32