Autocrine growth inhibition of a cloned line of helper T cells.
The growth of T lymphocytes is dependent on the T-cell growth factor interleukin 2 (IL-2), which causes T cells bearing high-affinity receptors for IL-2 to proliferate. Most cloned helper-T-cell lines can be shown to both produce and respond to IL-2; thus, growth of such cells is by an autocrine mechanism. We report that the failure of the cloned murine T-cell line D10.G4.1 to respond to its own IL-2 results from the secretion, by the same cells, of a potent inhibitor of the IL-2-driven T-cell proliferative response. This inhibition can be overcome by increasing the number of IL-2 receptors expressed by the target cell. In the cloned T-cell line producing the inhibitory substance, this increase in IL-2 receptors is driven by the monokine interleukin-1. We propose that this inhibitor of IL-2 responses may play a role in preventing "bystander" activation of T cells by IL-2 released in vivo and could be a potent pharmacologic agent.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D002455:Cell Division / Q000187:drug effects; D002999:Clone Cells; D006131:Growth Inhibitors / Q000302:isolation & purification / Q000502:physiology*; D007376:Interleukin-2 / Q000494:pharmacology / Q000502:physiology*; D051379:Mice; D008806:Mice, Inbred AKR; D008807:Mice, Inbred BALB C; D008970:Molecular Weight; D011971:Receptors, Immunologic / Q000187:drug effects / Q000276:immunology; D015375:Receptors, Interleukin-2; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000187:drug effects / Q000502:physiology*
D000911:Antibodies, Monoclonal; D006131:Growth Inhibitors; D007376:Interleukin-2; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2