title: IL-4 increases IL-2 production by T cells in response to accessory cell-independent stimuli.
abstract: Freshly prepared, highly purified T cells from naive mice failed to produce IL-2 in response to soluble anti-CD3 antibody or to Con A and produced only small amounts of IL-2 in response to anti-CD3 coated on the surface of microwells. IL-2 production in response to soluble anti-CD3 or to Con A required the addition of accessory cells. By contrast, the addition of IL-4 strikingly enhanced the production of IL-2 by plate-bound anti-CD3-stimulated T cells in the absence or the presence of added accessory cells. Furthermore, anti-IL-4 mAb inhibited IL-2 production by anti-CD3-stimulated T cells, which indicates that endogenously produced IL-4 was important in IL-2 production by T cells to plate-bound anti-CD3. The capacity of IL-4 to enhance and of anti-IL-4 to inhibit IL-2 production in response to plate-bound anti-CD3 was also observed with both unstimulated T cells and with T cells that had been previously stimulated with anti-CD3 antibody. When activated T cells were restimulated with anti-CD3, the effect of IL-4 in enhancing IL-2 production was detectable within 6 to 8 h after restimulation. The effect of IL-4 on IL-2 production was not due to prolongation of survival or to enhanced proliferation of T cells. Northern blot analysis showed that T cells treated with anti-CD3 plus IL-4 had more than 10-fold more IL-2 mRNA than did T cells treated with anti-CD3 plus anti-IL-4; this was observed within 6 h of stimulation under certain circumstances. The increased level of IL-2 mRNA by IL-4 was achieved without any change in message half-life, suggesting that IL-4 enhances transcriptional activation of the IL-2 gene in such cells. These results lead to the conclusion that IL-4 has a critical role in IL-2 production in response to accessory cell-independent stimuli (plate-bound anti-CD3 antibody), although it is not essential to IL-2 production in response to accessory cell-dependent stimuli (soluble anti-CD3 and Con A).
authors.affiliation: Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: T
authors.initials: T
authors.lastname: Tanaka
authors.forename: S Z
authors.initials: SZ
authors.lastname: Ben-Sasson
authors.forename: W E
authors.initials: WE
authors.lastname: Paul
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000502:physiology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology; D017252:CD3 Complex; D002478:Cells, Cultured; D005260:Female; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000235:genetics; D015847:Interleukin-4 / Q000494:pharmacology*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D007376:Interleukin-2; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D015847:Interleukin-4