Interferon production by mitogen-stimulated human lymphocytes requires differentiation but not DNA synthesis

• Published in: Human immunology Vol. 13; no. 3; pp. 151 - 160
• Main Authors: Bhayani, Hansha R., Williams, Gwyn T., Johnstone, Alan P.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.1985
• Subjects: Aphidicolin; Bromodeoxyuridine - pharmacology; Bucladesine - pharmacology; Cell Differentiation - drug effects; Diterpenes - pharmacology; DNA - biosynthesis; Humans; Hydroxyurea - pharmacology; In Vitro Techniques; Interferon-gamma - biosynthesis; Lymphocyte Activation - drug effects; Lymphocytes - cytology; Lymphocytes - immunology; Lymphocytes - metabolism; Phytohemagglutinins - pharmacology; IFNγ; PBS; CPM; db-cAMP; TCA; DMSO; FBS; PHA; 3MB; IL-2; IU
• ISSN: 0198-8859; 1879-1166
• DOI: 10.1016/0198-8859(85)90008-4

Mitogens such as phytohemagglutinin (PHA) stimulate T lymphocytes to differentiate, proliferate, and produce lymphokines: e.g., interferon gamma (IFN γ) and interleukin-2 (IL-2). Induction of IFNγ is an early event in mitogenesis, accompanied by an increase in RNA and protein synthesis, and latter followed by DNA synthesis. Although, in general, good IFNγ inducers are good mitogens, we show here that DNA synthesis is not an obligatory requirement for the production of IFNγ. Aphidicolin and hydroxyurea, which completelyy inhibit DNA synthesis, do not significantly affect IFN production, whether added before, with, or after mitogen stimulation. Inhibitors of differentiation, however, affect DNA and IFN synthesis depending on their time of addition in relation to PHA. The inhibitors, 3-methoxybenzamide (3MB) and a group of compounds that affect cyclic nucleotide metabolism (theophylline, and dibutyryl cyclic AMP), had profound inhibitory effects of IFN production. However, bromodeoxyuridine ( (BUdR), also an inhibitor of differentiation in some systems, had very little effect on IFN production.