Interleukin 4 Suppresses Interleukin 2 and Interferon γ Production by Naive T Cells Stimulated by Accessory Cell-Dependent Receptor Engagement

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 90; no. 13; pp. 5914 - 5918
• Main Authors: Tanaka, Toshio, Hu-Li, Jane, Seder, Robert A., Barbara Fazekas de St. Groth, Paul, William E.
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 01.07.1993; National Acad Sciences
• Subjects: Animals; Antibodies; Antigen-Presenting Cells - physiology; Antigens; Biological and medical sciences; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - metabolism; Cell lines; Cells, Cultured; Cultured cells; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Immunobiology; Interferon-gamma - biosynthesis; Interleukin-2 - biosynthesis; Interleukin-4 - pharmacology; Interleukins; Ionomycin - pharmacology; Lymph nodes; Lymphocyte Activation; Messenger RNA; Mice; Mice, Inbred BALB C; Modulation of the immune response (stimulation, suppression); Spleen cells; T cell antigen receptors; T lymphocytes; T-Lymphocytes - drug effects; T-Lymphocytes - metabolism; Tetradecanoylphorbol Acetate - pharmacology; Antigen presentation; Immunomodulation; Cytokine; Rodentia; Accessory cell; Biosynthesis; Vertebrata; Interleukin 4; Mammalia; Interleukin 2; Mouse; T-Lymphocyte; Sensitization; Gamma interferon
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.90.13.5914

Interleukin 2 (IL-2) and interferon γ(IFN-γ) production by CD4+T cells and IFN-γ production by CD8+T cells from naive mice in response to soluble anti-CD3 and antigen-presenting cells (APCs) were strikingly inhibited by culture in the presence of IL-4. IL-4 decreased IL-2 and IFN-γ mRNA levels after 15-24 hr but gave relatively little decrease in these mRNAs at 6-12 hr after stimulation with soluble anti-CD3. A 16-hr preculture of T cells with anti-CD3, APCs, and IL-4 was sufficient to inhibit subsequent production of IL-2 and IFN-γ in response to restimulation in the absence of IL-4. Furthermore, IL-4 treatment of T cells purified 24 hr after stimulation inhibited their capacity to subsequently produce IL-2 in response to anti-CD3 and APCs, indicating that T cells were targets of IL-4-mediated inhibition. IL-4 blocked acute IL-2 production in response to a cytochrome c peptide of T cells derived from transgenic mice expressing T-cell receptors specific for cytochrome c but it did not block IL-2 production by such cells after they had been primed in vitro. Nor did IL-4 inhibit production of IFN-γ by cloned T cells in response to antigen and APCs or production of IL-2 and IFN-γ by naive T cells in response to phorbol ester and calcium ionophore. These results indicate that IL-4 strikingly inhibits IL-2 and IFN-γ production by naive T cells in response to accessory cell-dependent, receptor-mediated stimulation (i.e., soluble anti-CD3 and APCs or antigen and APCs) but does not inhibit accessory cell-independent stimulation of naive T cells or accessory cell-dependent receptor-mediated stimulation of recently primed T cells or cloned T-cell lines.