IL-6 and IL-1 synergize to stimulate IL-2 production and proliferation of peripheral T cells.
Purified T cells can be induced to proliferate and to produce the autocrine growth factor IL-2 with mAb to the TCR and costimulatory cytokines. In a previous report we demonstrated that human IL-6 stimulates IL-2 production and proliferation of purified T cells, in conjunction with the insolubilized anti-TCR V beta 8 mAb, F23.1. Here we show that when CD4+ T cells are rigorously purified to greater than 99% CD4+CD8-, they respond only weakly to F23.1 and IL-6. Instead, there is an additional requirement for IL-1, which dramatically synergizes with IL-6 to induce prolonged (greater than 7 days) proliferative responses and IL-2 production. Similar results were observed when the highly mitogenic anti-CD3 mAb 145-2C11 was substituted for F23.1. The proliferation induced by F23.1, IL-1, and IL-6 was substantially (greater than 80%) inhibited by a mAb to mouse IL-2, and was not inhibited by an anti-IL-4-mAb. In accordance with this finding, medium conditioned by the activated CD4+ cells contained large amounts of IL-2, which increased over a 7-day culture period. These results demonstrate that IL-6 and IL-1 stimulate T cell proliferation by inducing production of the autocrine growth factor IL-2. In addition, the two lymphokines must be present simultaneously for activation to occur. The possible roles of IL-6 and IL-1 in IL-2 gene regulation and in Ag-induced T cell activation are discussed.
Holsti
M A
MA
Center for Cancer Research, Massachusetts Institute of Technology, Cambridge 02139.
Raulet
D H
DH
D000276:Adjuvants, Immunologic / Q000502:physiology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D004357:Drug Synergism; D007375:Interleukin-1 / Q000502:physiology*; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000502:physiology; D015850:Interleukin-6 / Q000502:physiology*; D007700:Kinetics; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D007375:Interleukin-1; D007376:Interleukin-2; D015850:Interleukin-6