Intracellular polyamine biosynthesis is required for optimal cytolytic T lymphocyte (CTL) induction

Conference · Sat Mar 01 04:00:00 EST 1986 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:5417384

Bowlin, T L; McKown, B J; Sunkara, P S

An increase in the activity of ornithine decarboxylase (ODC), the first and rate-limiting step in polyamine biosynthesis, is one of the early biochemical events regulating lymphocyte mitogenesis. However, the role of intracellular polyamine biosynthesis in lymphocyte effector cell function has not been fully elucidated. Utilizing ..cap alpha..-difluoromethyl-ornithine (DFMO), an irreversible inhibitor of ODC, the authors have evaluated the effect of inhibition of intracellular polyamine biosynthesis on cytolytic T lymphocyte (CTL) induction. The experimental system utilized the concanavalin A (Con A) mediated polyclonal induction of CTL from nylon wool purified T cell populations. The addition of DFMO at the initiation of T cell stimulation with Con A completely abrogated ODC induction. Similarly, by 48 hrs of culture DFMO reduced putrescine and spermidine levels 96% and 91% respectively. DFMO reduced T cell proliferation (/sup 3/H-TdR incorporation) up to 60% in a dose dependent manner. Similarly DFMO treatment reduced CTL (Thy 1.2/sup +/) induction by greater than 50%. This observed reduction in CTL activity was completely reversible by the addition of exogenous putrescine. DFMO treatment did not alter the expression of the CTL response once generated. These results demonstrate that intracellular polyamine biosynthesis is required for optimal CTL induction.

• Research Organization: Merrell Dow Research Institute, Cincinnati, OH
• OSTI ID: 5417384
• Report Number(s): CONF-8604222-
• Conference Information: Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Journal Volume: 45:3
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AGGLUTININS
AMINES
AMINO ACIDS
ANIMAL CELLS
ANTIBODIES
BIOLOGICAL MATERIALS
BIOSYNTHESIS
BLOOD
BLOOD CELLS
BODY FLUIDS
CARBON-CARBON LYASES
CARBOXY-LYASES
CARBOXYLIC ACIDS
CELL PROLIFERATION
CONCANAVALIN
CONNECTIVE TISSUE CELLS
DECARBOXYLASES
DOSE-RESPONSE RELATIONSHIPS
ENZYME ACTIVITY
ENZYMES
HEMAGGLUTININS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LECTINS
LEUKOCYTES
LYASES
LYMPHOCYTES
MATERIALS
MITOGENS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORNITHINE
PUTRESCINE
SOMATIC CELLS
SPERMIDINE
SYNTHESIS
TRACER TECHNIQUES
TRITIUM COMPOUNDS