Recombinant interleukin 4 promotes the growth of human T cells.
Recently, we reported the isolation of a cDNA clone that encodes a polypeptide which has B cell and T cell growth factor activities. The amino acid sequence of this polypeptide deduced from the nucleotide sequence of the cDNA clone showed significant homology with mouse B cell stimulating factor-1. Because of its multiple biologic activities, it was designated interleukin 4 (IL-4). Here we describe the effects of supernatants of Cos-7 mouse cells transfected with the IL-4 coding cDNA clone in a mammalian expression vector, on human thymocyte T cells and T cell clones. The T cell growth-promoting effect of IL-4 on preactivated T cells was not inhibited by monoclonal antibodies against IL-2 or the IL-2 receptor, indicating that the IL-4 activity is independent from IL-2 or the IL-2 receptor. IL-4 induces a low proliferative response in thymocytes and peripheral blood lymphocytes, but the response was considerably enhanced by preactivation of the thymocytes or peripheral blood T cells. Both T4+ and T8+ antigen-specific proliferative and cytotoxic T cell clones and T3 natural killer clones proliferated in response to IL-4. But one of six T4+ and one of four T8+ T cell clones were consistently found to be unresponsive. The proliferative responses to IL-4 were always lower than those obtained with IL-2. Most of the T cell clones generally became unresponsive to IL-4 10 days after stimulation, but still responded well to IL-2. These results indicate that the responsiveness to IL-4 is relatively short lasting and is regulated by activation signals. Interestingly, IL-4 acted in synergy with IL-2 in promoting the growth of T cell clones. Our results establish that IL-4 can act as a T cell growth factor independently of IL-2.
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D003208:Concanavalin A / Q000494:pharmacology; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000494:pharmacology*; D010835:Phytohemagglutinins / Q000494:pharmacology; D011994:Recombinant Proteins; D013601:T-Lymphocytes / Q000166:cytology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013950:Thymus Gland / Q000166:cytology
D006133:Growth Substances; D007376:Interleukin-2; D008222:Lymphokines; D010835:Phytohemagglutinins; D011994:Recombinant Proteins; D003208:Concanavalin A; D015847:Interleukin-4; D013755:Tetradecanoylphorbol Acetate