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AbstractAbstract
[en] Accumulation of adenosine (Ado) and/or deoxyadenosine (dAdo) in adenosine deaminase deficiency is thought to mediate the immunodeficiency associated with the genetic disease in humans. To study the mechanism by which immune function is impaired, we are using analogs which are not substrates for the deaminase. The analogs and their doses (mg/kg/day, IP) are: an Ado analog, Tubercidin (2); and two dAdo analogs, 2-chlorodeoxy-adenosine (50) and 2-fluoro, arabinosyl AMP (250). CTL were generated by injecting C57B1/6 mice with 2.5 x 107 P815 mastocytoma cells, IP. Groups of mice were then treated once daily on days 9-11 with the analogs. On day 12, the animals were sacrificed and spleen cell suspensions were enriched for CTL by passage through nylon wool columns. CTL were measured against 51Cr-labeled P815 targets using a standard 51Cr-release assay. Primary antibody response was assessed in AKR mice following immunization with a T-dependent (sheep erythrocytes) or T-independent (TNP-Ficoll) antigen. Animals were treated with the analogs on days 1-3. On day 4, spleen cells were removed and assayed for antibody response in a plaque-forming assay. The dAdo analogs, but not tubercidin, inhibited the immune functions at these near-maximally tolerated doses. Treatment of the mice with the deaminase inhibitor, deoxycoformycin (1 mg/kg/day), was not inhibitory to these responses
Primary Subject
Source
70. annual meeting of the Federation of American Society for Experimental Biology; St. Louis, MO (USA); 13-18 Apr 1986; CONF-8604222--
Record Type
Journal Article
Literature Type
Conference
Journal
Federation Proceedings. Federation of American Societies for Experimental Biology; ISSN 0014-9446; ; CODEN FEPRA; v. 45(4); p. 865
Country of publication
ANIMAL CELLS, ANIMALS, BETA DECAY RADIOISOTOPES, BIOLOGICAL MATERIALS, BLOOD, BLOOD CELLS, BODY FLUIDS, CHROMIUM ISOTOPES, CONNECTIVE TISSUE CELLS, DAYS LIVING RADIOISOTOPES, DISEASES, ELECTRON CAPTURE RADIOISOTOPES, EVEN-ODD NUCLEI, INTERMEDIATE MASS NUCLEI, ISOTOPE APPLICATIONS, ISOTOPES, LEUKOCYTES, MAMMALS, MATERIALS, NUCLEI, NUCLEOSIDES, NUCLEOTIDES, ORGANIC COMPOUNDS, RADIOISOTOPES, RIBOSIDES, RODENTS, SOMATIC CELLS, VERTEBRATES
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