Two distinct signals regulate induction of IL-2 responsiveness in CD8+ murine T cells.
In the model system used here, cross-linking of T-cell receptor structures (TCR) by antigen-presenting cells (APCs) is substituted by the use of anti-F23.1 anti-T-cell receptor monoclonal antibody immobilized on Sepharose beads. We show that CR cross-linking of resting murine CD8+ T cells seeded at low cell densities is insufficient to induce responsiveness to the growth-promoting effect of interleukin-2 (IL-2), i.e. fails to induce expression of functional IL-2 receptors. The macrophage cell-line product, IL-2 receptor-inducing factor (RIF), but not IL-1, IL-3, IL-4 and interferon-gamma (IFN-gamma) functions efficiently as a co-stimulator. Once activated, growth of CD8+ T cells is driven entirely by IL-2. We conclude that two restriction points control the activation of resting CD8+ T cells. While cross-linking of TCR is essential as the first step, RIF is required as the competence factor to induce IL-2 responsiveness. We consider the possibility that the ability of APCs to produce RIF determines the immunogenicity of APCs towards antigen-reactive resting CD8+ T cells.
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D016827:CD8 Antigens; D002455:Cell Division; D016207:Cytokines; D007376:Interleukin-2 / Q000494:pharmacology*; D008213:Lymphocyte Activation; D051379:Mice; D008815:Mice, Inbred Strains; D009363:Neoplasm Proteins / Q000494:pharmacology; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
D000945:Antigens, Differentiation, T-Lymphocyte; D016827:CD8 Antigens; D016207:Cytokines; D007376:Interleukin-2; D009363:Neoplasm Proteins; D011948:Receptors, Antigen, T-Cell; C055533:adult T cell leukemia-derived factor