@article{9c031f88acb64084838564adabbd2c37,
title = "Adenosine 5′-triphosphate (ATP)-mediated stimulation and suppression of DNA synthesis in lymphoid cells. II. Suppressive effect of ATP on murine T-cell functions",
abstract = "The suppressive effects of ATP on murine T-cell functions were studied. The suppressive effects of ATP as well as adenosine on the DNA synthesis of spleen cells are due to the presence of mature T-cells, because ATP has no suppressive effect on athymic nu/nu spleen cells. Further characterization of the cells which are responsible for ATP-mediated suppression of DNA synthesis revealed that the cells are nylon wool-adherent T-cells and PHA-reactive T-cells. In addition, the suppressive effects of ATP on both spontaneous and mitogen-induced proliferative responses are stronger than that of adenosine, and T-cells are more sensitive to ATP than B-cells. The observation that both ATP and adenosine have unique effects on T-cells compared to B-cells may contribute toward explaining why patients with severe combined immunodeficiency (SCID) associated with adenosine deaminase (ADA) deficiency have greater T-cell than B-cell abnormalities.",
author = "Susumu Ikehara and Good, {Robert A.} and Modak, {Mukund J.} and Pahwa, {Rajendra N.}",
note = "Funding Information: The metabolism of purine nucleotides and nucleosides is of special importance to lymphocyte function and differentiation. Two inherited disorders of purine metabolism, adenosine deaminase (ADA)3(EC 3. 5. 4.4) and purine nucleoside phosphorylase (EC 2.4. 2. 1) deficiency, have been reported to be associated with immunodeficiency diseases (Giblett, Anderson, Cohen, Pollara & Meuwissen, 1972; Giblett, Amman, Wara & Diamond, 1975). However, the reason that these enzyme deficiencies cause such severe effect on the immunological system is not known. A hypothesis to explain this association in ADA deficiency has assumed that adenosine and/or deoxyadenosine were in some way toxic (Carson, Kaye & Seegmiller, 1977; Cohen, Hirschorn, Horowitz, Rubinstein, Polmar, Hong & Martin, 1978; Simmonds, Panayi & Corrigall, 1977; Coleman, Donofrio, Hutton, Hahn, Daoud, Lampkin & Dyminski, 1978). Exogenous adenosine has been demonstrated to inhibit the mitogen-induced proliferation of cultured normal human lymphocytes, an effect markedly potentiated by ADA inhibitors (Coleman, et al., 1978; Hirschhorn, Grossman & Weissman, 1970; Carson & Seegmiller, 1976; Snyder, Mendelsohn & Seegmiller, 1976). Recently, considerable literature has also accumulated on the relationship of ATP and ADA deficiency: ATP and 2'-deoxyadenosine 5'-triphosphate (dATP) levels are elevated in lymphocytes of patients with ADA deficiency, and the elevation of ATP and dAPT produces suppressive effects on lymphocyte functions by inhibiting ribonucleotide reductase and DNA synthesis (Agarwal, Crabtree, Parks, Nelson, Keightley, Parkman, Rosen, Stern & Polmar, 1976; Schmalstieg, Nelson, Mills, Monahan, Goldman & Goldblum, 1977). In contrast, Gregory & Kern (1978) recently reported that ATP as well as adenosine had a stimulatory effect on mouse thymocytes. We have reported that ATP as well as adenosine enhance DNA synthesis of immature thymocytes or precursor T-cells in bone marrow which contain terminal deoxynucle-otidyl transferase (TdT), whereas ATP and adenosine inhibit DNA synthesis of the cells from spleen, lymph * This work was supported by grants from the National Institutes of Health, CA-08748, CA-17404, CA-19267, AI-11843, NS-11457, and AG-00541; by the Judith Harris Selig Memorial Fund, the Zelda Radow Weintraub Cancer Fund, and Research Career Development Award No. 1 KO4-CA-00545. t Address for reprints: Dr. R. N. Pahwa, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, N.Y. 10021, U.S.A. Abbreviations used in this paper: ATP, adenosine 5'-triphosphate; ADA, adenosine deaminase; dATP, 2'-deoxyadenosine 5 '-triphosphate; GTP, guanosine 5'-triphosphate; CTP, cytidine triphosphate; TdT, terminal deoxynucleotidyl transferase; PHA, phytohemagglutinin; Con A, concanavalin A; LPS, Lipopolysaccharide; PBS, phosphate buffered saline; SRBC, sheep red blood cells; PFC, plaque-forming cell; MLC, mixed lymphocyte culture; SI, stimulation index.",
year = "1983",
doi = "10.1016/0192-0561(83)90050-4",
language = "English (US)",
volume = "5",
pages = "567--573",
journal = "International Immunopharmacology",
issn = "1567-5769",
publisher = "Elsevier",
number = "6",
}