Effects of adenosine derivatives on cytotoxic T lymphocyte (CTL) and primary antibody responses in mice

Conference · Tue Mar 04 23:00:00 EST 1986 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:6801986

Kandil, O; Nakic, M; Nelson, J A

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 10/sup 7/ 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 /sup 51/Cr-labeled P815 targets using a standard /sup 51/Cr-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.

• Research Organization: Univ. of Texas, Houston
• OSTI ID: 6801986
• Report Number(s): CONF-8604222-
• Journal Information: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Vol. 45:4; ISSN FEPRA
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
ADENOSINE
ANIMAL CELLS
ANIMALS
ANTIBODIES
BETA DECAY RADIOISOTOPES
BIOLOGICAL EFFECTS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CHROMIUM 51
CHROMIUM ISOTOPES
CONNECTIVE TISSUE CELLS
DISEASES
ELECTRON CAPTURE RADIOISOTOPES
EVEN-ODD NUCLEI
HEREDITARY DISEASES
IMMUNE REACTIONS
IMMUNITY
INTERMEDIATE MASS NUCLEI
ISOTOPE APPLICATIONS
ISOTOPES
LEUKOCYTES
LYMPHOCYTES
MAMMALS
MATERIALS
MICE
NUCLEI
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
PATHOGENESIS
RADIOISOTOPES
RIBOSIDES
RODENTS
SOMATIC CELLS
TRACER TECHNIQUES
VERTEBRATES